JP2019518568A - Fiber-reinforced biocomposite medical implant with high mineral content - Google Patents

Abstract

A medical implant comprising a plurality of layers, each layer comprising a polymer and a plurality of unidirectionally arranged continuous reinforcing fibers. [Selected figure] Figure 32b

Description

Background art
Implant materials for permanent orthopedic implants Medical implants can be manufactured from metals, alloys, ceramics or degradable and stable composites. Stainless steel or titanium alloys are usually used in load bearing applications, ie in orthopedic applications requiring high strength. Metal implants have been successful for many years in use in orthopedic surgery, but also carry many risks for complications. Although these materials are inert, they are also used where the need for an implant is temporary, such as fracture fixation. In the case of metal bars and plates for fracture fixation, a second surgery to remove the instrument may be recommended approximately one year after confirmation of bone attachment. Implant removal poses additional risk to the patient, increasing morbidity, accounting for clinic availability and increasing overall treatment costs. If the device is not removed, it can cause bone remodeling. Furthermore, such remodeling can lead to bone fragility due to stress shielding or inflammation of the host tissue. Due to the high stiffness (elastic modulus) and strength of the metal compared to the stiffness and strength of cortical bone, stress shielding may occur, causing the metal to compress the bone and causing fracture or bone strength around the prostate. There is a risk of loss.

  Conventionally, bone plates, rods, screws, tacks, nails, clamps and pins for bone fixation and / or osteotomy, which fix bone fragments for treatment, as an example of a load-bearing medical implant constructed of metal alloys Can be mentioned. Other examples include cervical wedges for lumbar fusion and other operations in spinal surgery, lumbar cages and plates and screws.

For example, biostable polymers and composites thereof based on polymethacrylate (PMMA), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluoroethylene (PTFE), polyetheretherketone (PEEK), polysiloxanes and acrylic polymers , Has been used in the manufacture of medical implants. These materials are not biodegradable or bioabsorbable, and thus face the same limitations as many metals when used in medical implant applications, for example, they replace the implant at some point in the life of the implant Or it may require a second surgery to remove it. Furthermore, these materials are more brittle than metals (less strength and stiffness) so they are more susceptible to mechanical failure, especially after repeated dynamic loading (ie, due to material fatigue or creep) Become.
Medical implants for existing degradable polymers

Absorbable polymers have been used in the development of absorbable implants and may be referred to as absorbable, bioabsorbable or biodegradable implants. The advantage of using a biocompatible, absorbable polymer is that the polymer and thus the implant release non-toxic degradation products that are absorbed in the body and metabolized by the metabolic system. Polymers containing polylactic acid and polyglycolic acid and polydioxane have absorbency currently used as orthopedic plates, rods, anchors, pins or screws for non-load bearing medical implant applications such as craniofacial applications It is a biocompatible material. These medical implant materials offer the advantage of ultimate absorption and eliminate the need for later removal while converting stress to reconstruction from fractures. However, current bioabsorbable materials and implants do not have mechanical properties comparable to metal implants. The mechanical strength and modulus (approximately 3 to 5 GPa) of non-reinforced absorbable polymers are insufficient to support fractured cortical bone with a modulus in the range of approximately 15 to 20 GPa (Snyder SM et al. The flexural modulus of human tibia was measured to be about 17.5 GPa, Snyder SM Schneider E, Journal of Orthopedic Research, Vol. 9, 1991, pp. 422-431). As such, the application of existing medical implants constructed of absorbable polymers is limited and their fixation usually requires protection from movement or heavy loads. These devices are only considered when fixation of a low stress area such as a capsular fracture, ligament fixation, craniofacial or osteochondral fracture of a pediatric patient or adult is required (i.e. non-load bearing applications).
Reinforced degradable polymer material

Recently, reinforced polymeric materials with improved strength and stiffness (modulus of elasticity) have been introduced. These biodegradable composites usually comprise polymers reinforced by fillers in the form of fibres. In composites, a relatively flexible matrix (i.e., a polymer) is usually combined with the stiffening and strength reinforcing material to improve the mechanical properties of the composite matrix. For example, biodegradable glass or mineral materials can be used to improve the stiffness and strength of the biodegradable polymer matrix. In the prior art, several attempts to produce such composites have been reported, using bioactive glass particles, hydroxyapatite powder or short glass fibers to improve the properties of biodegradable polymers The In most cases, the strength and stiffness of these composites are lower than cortical bone or lower than cortical bone after rapid degradation in the physiological environment. As such, most of these composites are not suitable for use in load bearing medical implant applications. Recently, however, biodegradable composites having strength and stiffness equal to or higher than that of cortical bone, such as biodegradable composites comprising a biodegradable polymer and 20 to 70% by volume of glass fibers (WO2010128039 A1) ,It has been reported. For example, other composite implants formed of fiber reinforced polymers are disclosed in US Patents 4,750,905, 5,181,930, 5,397,358, Nos. 5,009,664, 5,064,439, 4,978,360 and 7,419,714, the disclosures of which are incorporated herein by reference. Be
Degradation mechanism of reinforced degradable polymer material

  When biodegradable composites are used for load bearing medical implant applications, such as to fix fractures, the mechanical properties of the medical implant have to be maintained for a long time. The degradation of the composite material leads to an early loss of strength or stiffness of the implant, which may lead to dysfunction of the implant, such as inadequate bone healing as a result of insufficient fixation of bone fragments.

  Biodegradable composites initiate hydrolysis when in contact with body fluids. This degradation may be the result of the degradation of the biodegradable polymer, the reinforcing filler or both. In particular, such degradation can lead to a rapid drop in mechanical strength and stiffness of certain reinforced polymeric materials reinforced with inorganic compounds in an aqueous environment, such as a physiological environment. If the resorbable polymer matrix is an organic material and the filler is an inorganic compound, the adhesion between the resorbable polymer matrix and the filler is reduced by the degradation of either the polymer or the filler in an aqueous environment, and rapidly The initial mechanical properties of the degraded and reinforced polymer may drop rapidly and be less than desirable adequate load bearing performance. Aside from the individual degradation of the polymer and the filler, the poor interaction and adhesion of the polymer and the reinforcement interface can lead to premature failure at the interface in an aqueous environment, whereby the reinforcement is removed from the polymer When released and the reinforcing effect of the filler is lost, a rapid drop in mechanical properties results.

  Tormala et al. (WO 2006/114483) describe a composite containing two reinforcing fibers, one polymer and one ceramic in a polymer matrix and has a good initial equivalent to that of cortical bone. The mechanical results (bending strength of 420 +/- 39 MPa and bending modulus of 21.5 GPa) are reported. However, the prior art teaches that bioabsorbable composites reinforced with absorbable glass fibers have a high initial flexural modulus, but their strength and modulus are rapidly lost in vitro .

  Improved interfacial bonding (such as covalent bonding) between the polymer and the reinforcement can significantly prolong the retention of the mechanical properties of the reinforced bioabsorbable polymer in an aqueous environment (WO 2010 1280 39 A1) but the polymer, the reinforcement or Due to the continuous hydrolysis between the two interfaces, the mechanical properties will be lost over time. Because osteointegration may take months or more, the long-term degradation profile of the mechanical properties of covalently reinforced bioresorbable polymers is the optimum for medical implants used for load bearing orthopedic applications May not be sufficient for

  An example of strength loss in implants of reinforced degradable polymers is described in connection with self-reinforcing poly-L-lactic acid (Majola A et al., Journal of Materials Science Materials in Medicine, Vol. 3, 1992 , Pp. 43-47). Thus, the strength and strength retention of the self-reinforcing poly-L-lactic acid (SR-PLLA) composite material bar was evaluated after intramedullary and subcutaneous implantation in rabbits. The initial bending strength of the SR-PLLA bar was 250 to 271 MPa. The flexural strength of the SR-PLLA implant after 12 weeks of intramedullary and subcutaneous implantation was 100 MPa.

It is interesting to tailor the polymers that are optimal for absorbent composites for medical devices, for copolyesters and terpolyesters of PLA, PGA and PCL. The choice of monomer ratio and molecular weight significantly affects the strength elasticity, modulus, thermal properties, degradation rate and melt viscosity of the absorbent composite, all of these polymers in vitro and in vivo. It is known to be degradable under both aqueous conditions in vivo. Two steps have been identified in the degradation process; first, degradation proceeds by random hydrolytic chain scission of the ester bond which reduces the molecular weight of the polymer. In the second stage, measurable weight loss is observed in addition to strand scission. The mechanical properties are at least significantly reduced at the point when the majority is lost or weight loss begins. The degradation rates of these polymers differ depending on the polymer structure: crystallinity, molecular weight, glass transition temperature, block length, racemization and chain construction (Middleton JC, Tipton AJ, Biomaterials 21, 2000, 2335-2346).
Unresolved issue of mineral content in orthopedic implants

  As mentioned above, attempts have been made to manufacture orthopedic fixation implants from bioresorbable polymers such as polylactic acid (PLA). However, the mechanical properties of these implants are simply derived from the PLA acidic polymer chains. Therefore, their strength is limited (part of bone strength and modulus), and the acid burst degradation process of these bioabsorbable polymer implants results in problematic local tissue responses (cysts, abscesses etc) The Bone adhesion to these implants was inadequate.

  The manufacturer responded to the inflammatory local tissue response and bone adhesion failure of the bioresorbable fixation device by mixing various mineral compositions into the bioresorbable polymer composition. For mineral compositions, companies have used mineral or mineral compositions having osteoconductivity. Some use tricalcium phosphate, some use hydroxyapatite, some use calcium sulfate and some use a mixture of these. These mixed composition implants are referred to as "biocomposite" implants, which incorporate 25-35% of minerals and the mineral powder is uniformly distributed in the polymer composition.

  Unfortunately, the mechanical strength of these implants is derived from bioresorbable polymers, and mineral additives in these biocomposite implants are due to the low amount of polymer in the implant when the mineral composition is added. Reduces the mechanical properties of the implant. Thus, biocomposite implants tend to be more brittle than comparable implants consisting entirely of bioabsorbable polymers. Due to the lack of mechanical properties of the implant, it is not possible to use more mineral than the existing 25-35%.

  On the other hand, without mineral composition, problems arise as a result of long-term implantation in existing biocomposite implants. These implants suffer from the inflammatory tissue response that still plagues bioabsorbable polymer implants. For example, for an ACL interference screw consisting of a biocomposite composition, the biocomposite screw has been shown to have a very high percentage of inflammatory reactions (cysts, edema) (Cox CL et al. J Bone Joint Surg Am. 2014; 96: 244-50). Furthermore, they do not promote biointegration very much. The article concludes, "These new generations of bioabsorbable screws are designed to promote bone integration, but no hole narrowing has been observed."

  Besides these inflammatory problems, current biocomposite screws also lack sufficient mechanical properties (Mascarenhas et al. Arthroscopy: J Arthroscopic & Related Surg 2015: 31 (3): pp 561-568) . In this article, "the main findings of this study are the prolongation of knee exudation, the increase of femoral bone foramen expansion and the increase of screw breakage with the use of a bioresorbable interference screw" I conclude.

  At the mechanical level, higher proportions of the mineral composition in the biocomposite implant may result in poor mechanical results, in particular resulting in mechanical results inferior to those of implants consisting only of bioresorbable polymers. There is. For example, the influence of different proportions of β-tricalcium phosphate (βTCP) has been considered for the mechanical properties of PLA-based biocomposites (Ferri JM et al. J Composite Materials. 2016; 0 (0): 1- 10).

  In this study, it was shown that the higher the proportion of βTCP, the significantly lower the tensile strength of PLA-βTCP biocomposites, a reference of which is shown in FIG.

  Furthermore, an increase in the fraction of βTCP results in a significant reduction in the amount of energy that the biocomposite can absorb, measured as Charpy impact energy. This is a very important parameter in orthopedic implants as an important property of orthopedic implants is their ability to withstand impact without fractures. This problem is illustrated in Table 2 (cited from the above reference).

  Used for load-bearing medical implant applications, such as structural fixation for load-bearing purposes, where the high strength and stiffness of the implant is maintained at least as high as cortical bone for at least the maximum healing time of the bone There is a great need for an enhanced bioabsorbable polymeric material that exhibits improved mechanical properties.

  It is known in the art that the construction of biocomposite fiber reinforcement materials with the necessary high strength and stiffness is a difficult problem for which no suitable solution has been obtained so far.

  Among such fiber-reinforced composite materials, achieving the high strength and stiffness required for many medical implant applications requires high mineral content from either continuous fibers or short fibers or long fiber reinforcements. It may require the use of fiber reinforcement having a rate. This is a significant difference from the implant structure, construction, design and manufacturing techniques used so far for medical implants made from composites containing polymers or low mineral content particles or short fiber reinforced polymers. Produces These implants are most commonly manufactured using injection molding or sometimes using 3-D printing manufacturing techniques.

  Unlike bulk materials, the properties of parts made of composite materials are highly dependent on the internal structure of the part. This is an already established principle in the design of parts from composite materials where the mechanical properties of fiber reinforced composites are known to depend on the angle and orientation of the fibers within the composite parts.

  Most of the designs in conventional composite parts have focused exclusively on the mechanical properties of the parts. However, these parts were permanent parts and were not degradable or absorbable. Therefore, it was not necessary to pay attention to the decomposition or absorption mechanism in the composite material in the part. Even conventional orthopedic implants composed of composites largely follow these same classic composite design principles.

  However, the invention relates to a medical implant consisting of a new kind of composite material which is biocompatible and often bioresorbable. The design challenges in the preparation of medical implants using these materials involve not only the mechanical properties that have been discussed in the composite parts, but also more aspects and parameters.

  Furthermore, for bioabsorbable fiber reinforced composite implants, the degradation profile of the composite within the implant also initially enhances both strength and stiffness over the period the fibers function early in the implant and also in the body of the device. You must consider making sure that it brings.

  Mechanical properties of great importance to the performance of the medical implant according to the invention include bending, tension, shear, compressive and torsional strength and stiffness (modulus of elasticity). In these bioabsorbable medical implants, these properties are very important both at time zero (i.e. in the implant after manufacture) and in the period after implantation in the body. As with the previously described parts made of fiber reinforced composites, the mechanical properties at time zero depend on the alignment and orientation of the fibers in the part. However, maintaining most of the mechanical properties after implantation (or simulated implantation) in the body requires additional and different considerations.

  As discussed in more detail below, such considerations for the design of medical implants include the following parameters: composition, component ratio (including mineral content in particular), fiber diameter, fiber distribution, fiber length, fiber alignment And fiber orientation and the like.

These parameters can influence several additional aspects and properties of the performance of the medical implant described herein:
1. Material degradation rate (decomposition products, local pH and ion levels during degradation)
2. Surface characteristics affecting interface between implant and surrounding local tissue Biological effects such as antibacterial or osteoconductive 4. Response to sterilization processes (such as ethylene oxide gas, gamma or electron beam radiation)

  The present invention, in at least some embodiments, is a great step forward from conventional implants in that they can achieve sustainable high load-bearing strength and stiffness, from fiber reinforced biocompatible composites Providing an implant composition provides a solution to these problems. Furthermore, in many embodiments of the present invention, these high strength levels are further enhanced by low volume effective implants. In addition, the biocomposites described herein are also optionally and preferably bioresorbable.

  Thus, the present invention overcomes the limitations of conventional approaches and features a fiber reinforcement, which comprises a biocomposite composition (optionally biodegradable), which maintains mechanical strength and stiffness over time. Provide an implant.

  The present invention, in at least some embodiments, provides a medical implant consisting of a biocomposite composition having a high mineral content and even superior mechanical properties, for conventional biocomposite medical applications Further overcome the limitations of implants. Preferably, the mineral composition is provided by reinforcing fibers made of a mineral composition.

  Preferably, the weight percent of the mineral composition in the biocomposite medical implant is in the range of 40-90%, more preferably 40% -70%, more preferably 40%. An even more preferred weight percent is in the range of 45% to 60%.

  Surprisingly, the inventors have found that such high mineral content or content makes it possible to obtain an implant with excellent mechanical properties.

  Furthermore, prior attempts to construct implants with higher mineral content failed because biocomposite implants were typically injection molded. Injection molding is more difficult with the flow characteristics of composites having mineral content or content in the high range described above.

  These preferential ranges derive from the very important balance between biocompatibility (rest of the inflammatory response) and high mechanical properties. As mentioned above, high mineral content in medical implants is potentially beneficial to increase the biocompatibility and safety profile of the implant and surrounding tissue, especially bone tissue. However, mineral content that is too high can lead to an undesirable reduction in mechanical properties. A decrease in the mechanical properties of the implant may be observed immediately. In other cases, due to the high mineral content, the implant loses its mechanical properties at an accelerating rate, thereby providing mechanical fixation over an in vivo period sufficient to support healing of the tissue, particularly orthopedic tissue. Losing its ability to provide an accelerated mechanical disassembly process can result.

  Preferably the density of the biocomposite composition for use in the present invention is between 1 and 2 g / mL. More preferentially, the density is between 1.2 and 1.9 g / mL. Most preferentially, it is between 1.4 and 1.8 g / mL.

  Preferably, the mineral content is provided by reinforced mineral fibers made of a mineral composition.

  If desired, the diameter of the reinforcing fibers for use with the enhanced biocomposite medical implant herein may be in the range of 1 to 100 μm. Preferably, the fiber diameter is in the range of 1 to 20 μm. More preferably, the fiber diameter is in the range 4 to 16 μm, most preferably in the range 9 to 14 μm.

  The standard deviation of the fiber diameter between fibers in the medical implant is preferably less than 5 μm, more preferably less than 3 μm and most preferably less than 1.5 μm. The uniformity of fiber diameter is beneficial for consistent properties throughout the implant.

  In one embodiment, the reinforcing fibers are fiber portions within the polymer matrix. Preferably, such fiber parts are on average 0.5 to 20 mm in length, more preferably the fiber part length is in the range of 1 to 15 mm, more preferably in the range of 3 to 10, And most preferably in the range of 4-8 mm.

  Optionally and preferably, the mineral composition is provided in the form of a sufficiently high amount and reinforcing fibers present in a sufficiently high mineral amount to provide the above weight percent mineral composition in the implant.

  The overall structure of the implant may be heterogeneous and / or amorphous, as desired. If non-uniform, the structure may be continuous in its properties, if desired. Alternatively, the implant may be divided into layers as desired.

  According to at least some embodiments, there is provided a medical implant comprising a plurality of layers of biocomposites, said layers optionally comprising a polymer which is biodegradable and a plurality of unidirectionally arranged continuous reinforcing fibers. including. These layers may be amorphous or ordered, as desired. Optionally and preferably, the biodegradable polymer is incorporated into the biodegradable composite. Also optionally and preferably, the fibers are embedded in a polymer matrix comprising one or more bioabsorbable polymers.

  According to at least some embodiments, the composite layers each consist of one or more composite tapes, said tape optionally being a biodegradable polymer and a plurality of unidirectionally arranged continuous reinforcing fibers. Including. Optionally and preferably, the biodegradable polymer is incorporated into the biodegradable composite. Also optionally and preferably, the fibers are embedded in a polymer matrix comprising one or more bioabsorbable polymers.

  Optionally and preferably, the fiber reinforced biodegradable composite in the implant has a flexural modulus of more than 5 GPa and a flexural strength of more than 80 MPa.

  Preferably, the fiber reinforced biodegradable composite in the implant has a flexural strength in the range of 150 to 800 MPa, more preferably 150 to 400 MPa. The modulus of elasticity is preferably in the range of 5 to 27 GPa, more preferably 16 to 27 GPa.

  Preferably, the fiber reinforced composite within the implant retains a modulus of greater than 5 GPa after 8 weeks of implantation and a flexural strength of greater than 60 MPa after 8 weeks.

  Preferably, the fiber reinforced composite within the implant retains mechanical properties of a flexural modulus of more than 12 GPa and a flexural strength of more than 180 MPa after 5 days of pseudophysiological degradation.

  More preferably, the fiber reinforced composite within the implant retains mechanical properties of flexural modulus greater than 10 GPa and flexural strength greater than 120 MPa after 5 days of pseudophysiological degradation.

  The term "biodegradable" as used herein also refers to materials that are absorbable, bioresorbable or absorbable in the body.

Scanning electron microscope (SEM) image using a backscattered electron (BSE) detector on a cross section of a 6 mm pin having a fiber content of 50% by weight, such as that described in Example 1. The magnification of this image is 2,500x. This image shows a magnified view of a cross section of a reinforced mineral fiber 102 embedded within a bioabsorbable polymer matrix 104. The fiber diameter is shown in image 106. Scanning electron microscope (SEM) image using a backscattered electron (BSE) detector on a cross section of a 6 mm pin having a fiber content of 50% by weight, such as that described in Example 1. The magnification of this image is 2,500x. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. The distance between adjacent fibers is indicated by 202. Scanning electron microscope (SEM) image using a backscattered electron (BSE) detector on a cross section of a 6 mm pin having a fiber content of 50% by weight, such as that described in Example 1. The magnification of this image is 500x. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. Each layer 306, 308, 310 comprises reinforcing fibers 304 and has a constant thickness 302. Scanning electron microscope (SEM) image using a backscattered electron (BSE) detector on a cross section of a 6 mm pin having a fiber content of 50% by weight, such as that described in Example 1. The magnification of this image is 150x. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. Scanning electron microscope (SEM) image using a backscattered electron (BSE) detector on a cross section of a 6 mm pin having a fiber content of 50% by weight, such as that described in Example 1. The magnification of this image is 500x. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. The layers are separated by regions of bioabsorbable polymer matrix 502. Scanning electron microscopy (SEM) image using a backscattered electron (BSE) detector on a cross section of a 6 mm pin having a 70% by weight fiber content, such as that described in Example 1. The magnification of this image is 500x. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. The distance between adjacent fibers is shown. Scanning electron microscopy (SEM) image using a backscattered electron (BSE) detector on a cross section of a 6 mm pin having a 70% by weight fiber content, such as that described in Example 1. The magnification of this image is 500x. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. Scanning electron microscope (SEM) image using a secondary electron detector on an Au sputtered cross section of a 2 mm pin having a fiber content of 50% by weight, such as that described in Example 2. The magnification of this image is 2,000x. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. The fiber diameter is shown in the image. Scanning electron microscope (SEM) image using a secondary electron detector on an Au sputtered cross section of a 2 mm pin having a fiber content of 50% by weight, such as that described in Example 2. The magnification of this image is 2,000x. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. The distance between adjacent fibers is shown. Scanning electron microscope (SEM) image using a secondary electron detector on an Au sputtered cross section of a 2 mm pin having a fiber content of 50% by weight, such as that described in Example 2. The magnification of this image is 1,000 ×. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. Scanning electron microscope (SEM) image using a secondary electron detector on an Au sputtered cross section of a 2 mm pin having a fiber content of 50% by weight, such as that described in Example 2. The magnification of this image is 5,000x. This image shows a magnified view of a cross section of a reinforced mineral fiber 1102 embedded within a bioabsorbable polymer matrix 1104. Scanning electron microscope (SEM) image using a secondary electron detector on an Au sputtered cross section of a 2 mm pin having a fiber content of 50% by weight, such as that described in Example 2. The magnification of this image is 1,000 ×. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. The layers are separated by regions of the bioabsorbable polymer matrix. Scanning electron microscope (SEM) image using a secondary electron detector on a Au sputtered cross section of a 2 mm cannulated pin with a fiber content of 50% by weight, such as that described in Example 2. The magnification of this image is 1,000 ×. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. The fiber diameter is shown in the image. Scanning electron microscope (SEM) image using a secondary electron detector on a Au sputtered cross section of a 2 mm cannulated pin with a fiber content of 50% by weight, such as that described in Example 2. The magnification of this image is 1,000 ×. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. The distance between adjacent fibers is shown. Scanning electron microscope (SEM) image using a secondary electron detector on a Au sputtered cross section of a 2 mm cannulated pin with a fiber content of 50% by weight, such as that described in Example 2. The magnification of this image is 1,000 ×. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. Scanning electron microscope (SEM) image using a secondary electron detector on a Au sputtered cross section of a 2 mm cannulated pin with a fiber content of 50% by weight, such as that described in Example 2. The magnification of this image is 1,000 ×. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. The layers are separated by regions of the bioabsorbable polymer matrix. Scanning electron microscopy (SEM) image using a backscattered electron (BSE) detector on a cross section of a 2 mm plate having a fiber content of 50% by weight, such as that described in Example 3. The magnification of this image is 1250x. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. The fiber diameter is shown in the image. Scanning electron microscopy (SEM) image using a backscattered electron (BSE) detector on a cross section of a 2 mm plate having a fiber content of 50% by weight, such as that described in Example 3. The magnification of this image is 1250x. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. The distance between adjacent fibers is shown. Scanning electron microscopy (SEM) image using a backscattered electron (BSE) detector on a cross section of a 2 mm plate having a 70% by weight fiber content, such as that described in Example 3. The magnification of this image is 250x. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. Each layer 1902, 1904 consists of fibers. The distance between adjacent fibers is shown. Scanning electron microscopy (SEM) image using a backscattered electron (BSE) detector on a cross section of a 2 mm plate having a 70% by weight fiber content, such as that described in Example 3. The magnification of this image is 250x. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. Scanning electron microscopy (SEM) image using a backscattered electron (BSE) detector on a cross section of a 2 mm plate having a 70% by weight fiber content, such as that described in Example 3. The magnification of this image is 500x. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within a bioabsorbable polymer matrix. The layers are separated by regions of the bioabsorbable polymer matrix. Scanning electron microscope (SEM) image using a secondary electron detector on an Au sputtered cross section of a 2 mm pin having a fiber content of 50% by weight, such as that described in Example 2. The magnification of this image is 300x. This image shows a magnified view of the longitudinal axis of the reinforcing mineral fiber 2202. Scanning electron microscope (SEM) image using a secondary electron detector on a Au sputtered cross section of a 2 mm cannulated pin with a fiber content of 50% by weight, such as that described in Example 2. The magnification of this image is 250x. This image shows a magnified view of the cannulation and continuous reinforcing mineral fibers. The tangent angle 2302 is defined as the deviation from the direction of the curve at a fixed starting point, the fixed starting point being the point at which the fiber contacts or is closest to the center of the circular area of the cross section It is. Scanning electron microscope (SEM) image using a secondary electron detector on an Au sputtered cross section of a 6 mm pin having a fiber content of 50% by weight, such as that described in Example 1. The magnification of this image is 500x. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded within the bioabsorbable polymer matrix and tightly bundled together within group 2402. Scanning electron microscope (SEM) image using a secondary electron detector on a Au sputtered cross section of a 2 mm cannulated pin with a fiber content of 50% by weight, such as that described in Example 2. The magnification of this image is 500x. This image shows a magnified view of the cross section of the reinforced mineral fiber surrounding the inner cannula of pin 2502. Scanning electron microscope (SEM) image using a secondary electron detector on a Au sputtered cross section of a 2 mm cannulated pin with a fiber content of 50% by weight, such as that described in Example 2. The magnification of this image is 1000x. This image shows a magnified view of the cross section of a reinforced mineral fiber embedded within the bioabsorbable polymer matrix layer in alternating orientations of 0 ° and 45 °. Scanning electron microscope (SEM) image using a secondary electron detector on an Au sputtered cross section of a 6 mm pin having a fiber content of 85% by weight, such as that described in Example 1. Magnification 160x. This image shows a magnified view of a cross section of a reinforced mineral fiber embedded in layer 2702 in alternating orientations of 0 ° and 45 ° with little or no bioabsorbable polymer matrix separating the layers. Scanning electron microscope (SEM) image using a secondary electron detector on an Au sputtered cross section of a 6 mm pin having a fiber content of 85% by weight, such as that described in Example 1. 1000x magnification. This image shows a magnified view of a cross section of a reinforced mineral fiber with little or no bioabsorbable polymer matrix surrounding the fiber. Scanning electron microscopy (SEM) image using a backscattered electron (BSE) detector on a cross section of a 2 mm pin having a fiber content of 50% by weight, such as that described in Example 2. 60x magnification. This image shows a magnified view of the end of the pin and shows that a bioabsorbable polymer is present on the outer surface of the implant 2902. Figure 1 illustrates one example of a continuous fiber reinforced tape of the type that can be used to form a layer in a medical implant consisting of a continuous fiber reinforced layer. An example of a cut away three dimensional view of a continuous fiber reinforced tape (200) is shown. An example of a top view of a reinforced bioabsorbable composite sheet (300) consisting of three layers of unidirectional fibers at different angles is shown. An example of a cutaway view of a reinforced bioabsorbable composite structure (310) consisting of three layers of unidirectional fibers at different angles is shown. Fig. 6 shows an example of a continuous fiber reinforced composite medical implant wall. Continuous fiber reinforced composite medical implant wall (500) further including perforations (502) that allow for tissue and cell ingrowth into bone filler material (504) contained within the bone filler cage An example of a bone filler cage consisting of An example of a bioresorbable cannulated screw (600), which is a medical implant, is shown.

  The medical implant according to at least some embodiments of the present invention is suitable for load bearing orthopedic implant applications and one or more biotypes, where sustained mechanical strength and stiffness are important for proper implant function The composite, optionally comprising a bioresorbable material, the implant further comprises a moisture-proof coating which limits or eliminates fluid exchange to the implant.

  Thus, the present invention, according to at least some embodiments, provides a medical implant useful as a structural anchor for load bearing purposes, which is persistent as a result of preventing degradation of the bioabsorbable material that comprises the implant. Mechanical characteristics.

  Related implants include bone fixation plates, intramedullary nails, joint (hips, knees, elbows) implants, spinal implants, suture anchors, screws, pins, wires, bone cage and fracture fixation, tendon reattachment, spine fixation, soft tissue repair And other devices for such applications, such as for spinal cages.

  According to at least some embodiments, the present invention relates to a medical implant consisting of a biocomposite composition. Preferably, the biocomposite composition consists of a (optionally bioresorbable) polymer reinforced by a mineral composition. Preferably, the mineral composition reinforcement is provided by reinforcing fibers made of a mineral composition. As mentioned above, the mineral content of the implant is preferably relatively high.

  Optionally, the medical implant, or a portion thereof, comprises multiple biocomposite layers, each layer comprising a bioabsorbable polymer reinforced by unidirectional reinforcing fibers. The properties of the implant are optionally and preferably determined according to the layer composition and structure and the arrangement of the layer with respect to the device, for example with respect to the layer direction. The fibers may, if desired, remain separated but, if desired, some melting of the polymer may occur to bond the layers together.

  The biocomposite layer can be defined as a continuous or semi-continuous layer over part or all of the medical implant, the layer consisting of reinforcing fibers arranged in one direction. The layers can be identified in several figures showing the internal structure of the reinforced biocomposite medical implant, including FIGS. 7, 10 and 20.

  Preferably, there are between 1 and 100 reinforcing fibers that form the thickness of each biocomposite layer. Preferably, there are between 2 and 40 reinforcing fibers within each layer thickness, and most preferably between 4 and 20 reinforcing fibers.

  If desired, the directional fiber orientation between adjacent layers in the implant will be staggered between layers such that each adjacent layer is out of phase (different angles) from the adjacent layer. Preferably, the average or median angle that differs between the layers is between 15 and 75 degrees, more preferably between 30 and 60 degrees, and most preferably between 40 and 50 degrees. Such heterophase adjacent biocomposite layer microscopy images can be confirmed in FIGS.

  Preferably, the biocomposite layers in the medical implant are in close proximity to one another. More preferably, the distance between the layers measured by the distance between the last fiber in one layer and the first fiber in the next layer is between 0 and 200 μm, more preferably between 0 and 60 μm, 1 to 40 μm and Most preferably it is between 2 and 30 μm. The close proximity of the fibers in the layer to the fibers in the adjacent layer allows each layer to mechanically support the adjacent layer. However, some distance between layers allows some polymers to remain between the fibers of adjacent layers, thus depositing the layers together and preventing the cleavage of the layer under high mechanical loading May be desirable.

  Optionally, the diameter of the majority of reinforcing fibers for use with the enhanced biocomposite medical implant herein is in the range of 1 to 100 μm. Preferably, the fiber diameter is in the range of 1 to 20 μm. More preferably, the fiber diameter is in the range of 4 to 16 μm and most preferably in the range of 9 to 14 μm.

  Optionally, the average diameter of the reinforcing fibers for use with the enhanced biocomposite medical implant herein is in the range of 1 to 100 μm. Preferably, the fiber diameter is in the range of 1 to 20 μm. More preferably, the fiber diameter is in the range of 4 to 16 μm and most preferably in the range of 9 to 14 μm.

  The standard deviation of fiber diameter between fibers in the medical implant is preferably less than 5 μm, more preferably less than 3 μm and most preferably less than 1.5 μm. The uniformity of fiber diameter is beneficial for consistent properties throughout the implant.

  In one embodiment, the reinforcing fibers are fiber portions within the polymer matrix. Preferably, such fiber portions are on average 0.5 to 20 mm in length, more preferably, the fiber portion length is in the range of 1 to 15 mm, more preferably in the range of 3 to 10 and Most preferably, it is in the range of 4 to 8 mm.

  Preferably, the majority of the reinforcing fiber parts are 0.5 to 20 mm in length, more preferably the fiber part length is in the range of 1 to 15 mm, more preferably in the range of 3 to 10 and most preferably Is in the range of 4 to 8 mm.

  If desired, the reinforcing fibers are continuous fibers. The continuous fibers are preferably longer than 5 mm, more preferably longer than 8 mm, 12 mm, 16 mm and most preferably longer than 20 mm. A microscope image of such continuous fibers can be seen in FIG.

  Alternatively or additionally, the length of the reinforcing fibers can be defined as a function of the length of the implant, at least some of the reinforcing fibers and preferably most of the reinforcing fibers being medical implants or their implants A continuous length of at least 50% of the longitudinal length of the medical implant component consisting of fibers. Preferably, some or most of the reinforcing fibers are at least 60% continuous and at least 75% long of the medical implant, more preferably of the medical implant. Such continuous reinforcing fibers can provide structural reinforcement to the majority of the implant.

  Optionally, the distance between adjacent reinforcing fibers in the biocomposite layer is in the range of 0.5 to 50 μm, preferably, the distance between adjacent fibers is in the range of 1 to 30 μm, more preferably 1 It is in the range of -20 μm and most preferably in the range of 1-10 μm.

  Preferably, the weight percent of reinforcing fibers (mineral composition) in the biocomposite medical implant is in the range of 40-90%, more preferably, the weight percent is in the range of 40% -70%, more preferably Preferably it is in the range 40% to 60%, and even more preferably the weight percent is in the range 45% to 60%.

  Preferably, the volume percent of reinforcing fibers in the biocomposite medical implant is in the range of 30-90%, more preferably, the volume percent is in the range of 40% to 70%.

  Optionally, the plurality of fibers in the implant are unidirectionally arranged. Optionally, the arrayed fiber portions are 5 to 12 mm in length on average.

  Preferably, the fibers arranged in one direction are arranged at the longitudinal access of the implant (0 ° alignment with respect to the longitudinal axis). Preferably, most of the fibers are aligned in one direction with the longitudinal axis. Optionally, 70%, 80%, 90%, more than 95% of the fibers are aligned in one direction with the longitudinal axis.

  Optionally, the plurality or majority of fibers in the implant are aligned with the longitudinal axis. Optionally, the plurality of fibers are arranged in up to three additional directions. Optionally, the plurality of fibers are arranged in the following alignment options with respect to the longitudinal axis: 0 °, 30 °, -30 °, 45 °, -45 °, 90 °. Preferably, the plurality of fibers are arranged in the following arrangement of orientations with respect to the longitudinal axis: 0 °, 45 °, -45 °, 90 °. More preferably, the plurality of fibers are arranged in the following arrangement of choices with respect to the longitudinal axis: 0 °, 45 °, -45 °.

  Optionally, most of the fibers are arranged at the longitudinal access of the implant, and the plurality of fibers are arranged in the following arrangement with respect to the longitudinal axis: 45 °, -45 °.

  Optionally, the fiber portion is arranged amorphous.

  While the biocomposite composition within the implant is important in determining the mechanical and bulk properties of the implant, the specific composition and structure in contact with the edge of the surface of the implant may be surrounding cells after implantation into the body And how the tissue interacts with the implant, it has particular significance in that this composition and structure can have a major impact. For example, the absorbable polymer portion of the biocomposite may be hydrophobic in nature and repel the surrounding tissue to some extent, while the mineral reinforcing fiber portion of the biocomposite may be hydrophilic in nature. The surrounding tissue adheres to the implant or is promoted to cause tissue ingrowth.

  In any of the embodiments of the present invention, the presence (percent of surface area) of one compositional component at the surface is greater than the volume percent of the component in the bulk composition of the implant. For example, the amount of mineral on the surface may be greater than the amount of polymer, or vice versa. While not wishing to be limited by a single hypothesis, a large amount of mineral will be present, as desired and preferably on the surface, in order to be firmly fused with the bone. In order to reduce bone fusion, a large amount of polymer will be optionally and preferably present on the surface. Preferably, the compositional percentage of surface area for one component is more than 10% greater than the percentage by volume of that component in the entire biocomposite implant. More preferably, the proportion is more than 30%, most preferably more than 50%. FIG. 25 shows a microscopic image of a biocomposite medical implant with an overwhelming amount of mineral reinforcing fibers along the edge of the implant's inner surface. FIG. 29 shows a microscopic image of a biocomposite medical implant with an overwhelming amount of bioabsorbable polymer along the outer surface of the implant.

  Optionally, one surface of the medical implant may have a local overwhelming amount of one biocomposite component, while different surfaces or different portions of the same surface may locally It may have different amounts of biocomposite components.

  Optionally, mineral content is absent at most surfaces (ie, most of the surface of the implant is covered with a polymer film). Optionally, the surface polymer film is on average 0.5 to 50 μm, more preferably 5 to 50 μm and most preferably 10 to 40 μm thick.

  Optionally, there are fibers exposed on the surface of the implant. Optionally, the exposed fibers constitute 1 to 60% of the implant surface. Optionally, the exposed fibers constitute 10 to 50% of the implant surface. Optionally, the exposed fibers constitute 15-30% of the implant surface.

  If desired, the medical implant is a threaded screw or other threaded implant. Preferably, the outer layer of the implant is aligned in such a way that the direction of the fibers approaches the twist angle of the threaded portion. Preferably, the alignment angle in the fiber direction is within 45 degrees of the twist angle. More preferably, the alignment angle is within 30 degrees of the twist angle, and most preferably, the alignment angle is within 15 degrees. In this way, by approximating the fiber arrangement to the angle of twist angle, it is possible to improve the robustness of the thread and to prevent the tearing of the reinforcing fibers in the thread.

  With respect to a circular implant, the reinforcing fibers may optionally take on the full circular shape of the implant and bend around the circular shape of the implant without departing from its circumference. Preferably, some or most of the reinforcing fibers deviate from the circular shape of the implant so as to form a tangent angle. The angle of the tangent is defined as the deviation from the direction of the curve at a fixed starting point, the fixed starting point being the point at which the fiber contacts or is closest to the center of the circular area of the cross section is there. FIG. 23 shows the angle of tangent of the reinforcing fiber to the cannulated circular pin.

  Preferably, the angle of tangent between the reinforcing fibers in the circular medical implant and the bend in the implant is less than 90 degrees, more preferably less than 45 degrees.

Preferably, the density of the biocomposite composition for use in the present invention is between 1 and 2 g / mL. More preferentially, the density is between 1.2 and 1.9 g / mL. Most preferentially, it is between 1.4 and 1.8 g / mL.
Bioabsorbable polymer

  In a preferred embodiment of the present invention, the biodegradable composite material comprises a bioresorbable polymer.

  The medical implants described herein may be made of any biodegradable polymer. The biodegradable polymers may be homopolymers or copolymers, including random copolymers, block copolymers or graft copolymers. Biodegradable polymers may be linear polymers, branched polymers or dendrimers. Biodegradable polymers may be of natural or synthetic origin. Examples of suitable biodegradable polymers include lactide, glycolide, caprolactone, valerolactone, carbonates such as trimethylene carbonate and tetramethylene carbonate, dioxanones such as 1,4-dioxanone, δ-valerolactone, 1 (Dioxepanone), for example, 1,4-dioxepan-2-one and 1,5-dioxepan-2-one), ethylene glycol, ethylene oxide, ester amide, γ-hydroxyvalerate, β-hydroxypropionic acid, α -Hydroxy acid, hydroxybuterate, poly (ortho ester), hydroxy alkanoate, tyrosine carbonate, polyimide carbonate, poly (bisphenol A-imi) Polymers such as carbonates) and poly (polyquinones such as hydroquinone-iminocarbonates, polyurethanes, polyanhydrides, polymeric drugs (eg, polydiflunisal, polyaspirin and protein therapeutics (as well as those made from copolymers and combinations thereof) Suitable natural biodegradable polymers include but are not limited to collagen, chitin, chitosan, cellulose, poly (amino acids), polysaccharides, hyaluronic acid, intestines, copolymers and their derivatives and combinations thereof The thing is mentioned.

According to the invention, the biodegradable polymer may be a copolymer or a terpolymer, for example polylactide (PLA), poly-L-lactide (PLLA), poly-DL-lactide (PDLLA); polyglycolide (PGA); glycolide Copolymer, glycolide / trimethylene carbonate copolymer (PGA / TMC); lactide / tetramethyl glycolide copolymer, lactide / trimethylene carbonate copolymer, lactide / d-valerolactone copolymer, lactide / ε-caprolactone copolymer, L-lactide / DL-lactide Copolymer, glycolide / L-lactide copolymer (PGA / PLLA), other copolymers of PLA such as polylactide-co-glycolide; lactide / glycolide / trimethylene carbonate terpolymer, Kuta / glycolide / ε-caprolactone terpolymer, PLA terpolymer such as PLA / polyethylene oxide copolymer; polydepsipeptide; unsymmetrical-3,6-substituted poly-1,4-dioxane-2,5-dione; polyhydroxyalkanoate Polyhydroxybutyrate (PHB) and the like; PHB / b-hydroxyvalerate copolymer (PHB / PHV); poly-b-hydroxypropionic acid (PHPA); poly-p-dioxanone (PDS); poly-d-valerolactone -Poly-ε-caprolactone, poly (ε-caprolactone-DL-lactide) copolymer, methyl methacrylate-N-vinylpyrrolidone copolymer, polyesteramide, polyester of oxalic acid, polydihydropyran, polyalkyl-2-cyanoacrylate Polyurethanes (PU); polyvinyl alcohol (PVA); polypeptides; poly-b-malic acid (PMLA): poly-b-alkanoic acids; polycarbonates; polyorthoesters; polyphosphates; And mixtures thereof; as well as natural polymers such as sugars; starches, celluloses and cellulose derivatives, polysaccharides, collagens, chitosans, fibrins, hyaluronic acids, polypeptides and proteins. Any of the above polymers and mixtures of their various forms may also be used.
Enhanced bioabsorbable polymer

  According to at least some embodiments of the present invention, a medical implant comprises a reinforced bioabsorbable polymer (i.e. comprising a polymer as described above and incorporating reinforcing fillers generally in fiber form, polymer mechanical Bioabsorbable composites) with increased mechanical strength.

  In a more preferred embodiment of the present invention, the reinforced bioabsorbable polymer is a reinforced polymer composition consisting of any of the above bioabsorbable polymers and a reinforcing filler, preferably in fiber form. Reinforcing fillers may consist of organic or inorganic (i.e. natural or synthetic) materials. The reinforcing filler may be biodegradable glass, cellulosic material, nano diamond or any other filler known in the art to increase the mechanical properties of the bioabsorbable polymer. The filler is preferably made of a material or type of material other than the bioresorbable polymer itself. However, it may also be fibers of the bioresorbable polymer itself, if desired.

  Many examples of such reinforced polymer compositions have already been documented. For example, a biocompatible and absorbable melt-inducing glass composition (EP 2 243 749 A1), which can embed glass fibers in a continuous polymer matrix, a biodegradable polymer and a biodegradable material comprising 20 to 70 vol% glass fibers Composite material (WO2010128039 A1), absorbable and biocompatible fiberglass (US 2012/0040002 A1) that can be embedded in a polymer matrix, biocompatible composite material and its use (US 2012/0040015 A1), poly as a filler Absorbent polymers containing [succinimide] (EP 0 671 177 B1).

  In a more preferred embodiment of the invention, the reinforcing filler is attached to the bioresorbable polymer such that the reinforcing effect is sustained for a long time. Such an approach is described in US 2012/0040002 A1 and EP 2243500 B1 and discusses composite materials comprising a biocompatible glass, a biocompatible matrix polymer and a coupling agent capable of forming a covalent bond. .

  As mentioned above, the biodegradable composite material and the fibers are preferably arranged in the form of layers of biodegradable composite material, each layer being embedded in a polymer matrix consisting of one or more bioabsorbable polymers It comprises continuous reinforcing fibers arranged in one direction.

  The biodegradable composite layer preferably consists of one or more biodegradable composite tapes, each of which is a unidirectionally arranged continuous embedded in a polymer matrix of one or more bioabsorbable polymers. Containing various reinforcing fibers.

  The biodegradable composite is preferably incorporated into the polymer matrix and may optionally include any of the above-mentioned polymers. Optionally and preferably, it is PLLA (poly-L-lactide), PDLLA (poly-DL-lactide), PLDLA, PGA (poly-glycolic acid), PLGA (poly-lactide-glycolic acid), PCL (polycaprolactone) ), PLLA-PCL, and combinations thereof. If PLLA is used, preferably the matrix comprises at least 30% PLLA, more preferably 50% and most preferably at least 70% PLLA. If PDLA is used, preferably the matrix comprises at least 5% PDLA, more preferably at least 10%, most preferably at least 20% PDLA.

  Preferably, the intrinsic viscosity (IV) (independent of the reinforcing fibers) of the polymer matrix is in the range of 1.2 to 2.4 dl / g, more preferably in the range of 1.5 to 2.1 dl / g, and most preferably Is in the range of 1.7 to 1.9 dl / g.

Intrinsic viscosity (IV) is a viscometric method for measuring molecular size. IV is based on the flow time of the polymer solution through the capillary relative to the flow time of the pure solvent through the thin capillary.
Reinforcing fiber

  Preferably, the reinforcing fibers consist of silica-based mineral compounds such that the reinforcing fibers comprise bioabsorbable glass fibers and may also be referred to as bioglass fiber composite materials.

  The mineral composition may include beta-tricalcium phosphate, calcium phosphate, calcium sulfate, hydroxyapatite or bioresorbable glass (also known as bioglass).

  Additional optional glass fiber compositions have already been described by Lehtonen TJ et al. (Acta Biomaterialia 9 (2013) 4868-4877), which is hereby incorporated by reference in its entirety; such glass fiber compositions are If desired, it may be used instead of or in addition to the above composition.

  Additional optional bioabsorbable glass compositions are described in the following patent applications and are incorporated herein as if fully described herein by reference: biocompatible composites and their Uses (WO2010122098); and absorbable and biocompatible fiberglass compositions and their use (WO2010122019).

  In a more preferred embodiment of the invention, the reinforcing filler is attached to the bioresorbable polymer such that the reinforcing effect is sustained for a long time. Such an approach is described in US 2012/0040002 A1 and EP 2243500 B1 and discusses composite materials comprising a biocompatible glass, a biocompatible matrix polymer and a coupling agent capable of forming a covalent bond. .

The bioabsorbable glass fibers may optionally have an oxide composition in the following mole% range:
Na ₂ O: 11.0 to 19.0 mol%
CaO: 9.0 to 14.0 mol%
MgO: 1.5 to 8.0 mol%
B ₂ O ₃ : 0.5 to 3.0 mol%
Al ₂ O ₃ : 0 to 0.8 mol%
P ₂ O ₃ : 0.1 to 0.8 mol%
SiO ₂ : 67 to 73 mol%

More preferably, it may have the following mole% range:
Na ₂ O: 12.0 to 13.0 mol%
CaO: 9.0 to 10.0 mol%
MgO: 7.0 to 8.0 mol%
B ₂ O ₃ : 1.4 to 2.0 mol%
P ₂ O ₃ : 0.5 to 0.8 mol%
SiO ₂ : 68 to 70 mol%

  Additional optional glass fiber compositions have already been described by Lehtonen TJ et al. (Acta Biomaterialia 9 (2013) 4868-4877), which is hereby incorporated by reference in its entirety; such glass fiber compositions are If desired, it may be used instead of or in addition to the above composition.

Additional optional bioabsorbable glass compositions are described in the following patent applications and are incorporated herein as if fully described herein by reference: biocompatible composites and their Uses (WO2010122098); and absorbable and biocompatible fiberglass compositions and their use (WO2010122019).
Optional additional features

  The following features and embodiments may be combined with any of the above features and embodiments as desired.

  The tensile strength of the reinforcing fibers is preferably in the range of 1200-2800 MPa, more preferably in the range of 1600-2400 MPa and most preferably in the range of 1800-2200 MPa.

  The modulus of the reinforcing fibers is preferably in the range of 30 to 100 GPa, more preferably in the range of 50 to 80 GPa and most preferably in the range of 60 to 70 GPa.

  The fiber diameter is preferably in the range of 6 to 20 μm, more preferably in the range of 10 to 18 μm and most preferably in the range of 14 to 16 μm.

  Optionally, the majority of reinforcing fibers arranged in the longitudinal axis of the medical implant have a length of at least 50%, preferably at least 60%, more preferably at least 75% and most preferably at least 85% of the total length of the implant It is.

  If desired, the fibers may be arranged at an angle (i.e., diagonally) to the longitudinal axis such that the length of the fibers can be more than 100% of the length of the implant. Optionally and preferably, the majority of reinforcing fibers are arranged at an angle of less than 90 °, alternatively less than 60 ° or optionally less than 45 ° from the longitudinal axis.

  Preferably, the implant comprises preferably between 2 and 20 composite tape layers, more preferably between 2 and 10 layers and most preferably between 2 and 6 layers; each layer in a different direction It may be aligned, or some of the layers may be aligned in the same direction as other layers.

Preferably, the maximum angle between the fibers in at least some layers is greater than the angle between the fibers in the respective layer and the longitudinal axis. For example, one layer of reinforcing fibers may be aligned and obliquely right with respect to the longitudinal axis, while another layer may be aligned left inclined with respect to the longitudinal axis.
Compatibilizer

Optionally and preferably, the composite material composition further comprises a compatibilizer, such as a compatibilizer as described in WO2010122098, as if fully described herein by reference. Incorporated herein by reference.
Alternative forms of biodegradable composites

  Alternatively, the biodegradable composite may comprise strands of composite comprising continuous reinforcing fibers or fiber bundles impregnated with a bioabsorbable polymer. Preferably, the strands are less than 1 cm in diameter. More preferably, the strands are less than 8 mm, less than 5 mm, less than 3 mm or less than 2 mm in diameter.

  Alternatively, the biodegradable composite may comprise a woven mesh of continuous reinforcing fibers, the woven mesh being pre-impregnated with a bioabsorbable polymer or a woven mesh being from reinforcing fibers And subsequently impregnated with a bioresorbable polymer.

Preferably, the mesh layer of the biodegradable composite material is less than 1 cm in thickness. More preferably, the impregnated mesh has a thickness of less than 8 mm, less than 5 mm, less than 3 mm or less than 2 mm.
Mineral content

  The present invention, in at least some embodiments, further provides a medical implant comprising a biocomposite composition having a high percentage of mineral content and further excellent mechanical properties. Overcome the limitations of implant implants. Preferably, the mineral composition is provided by reinforcing fibers made of a mineral composition.

  Preferably, the weight percent of the mineral composition in the biocomposite medical implant is in the range of 40-90%, more preferably, the weight percent is in the range of 40% -70%, even more preferably , Weight percent is in the range of 45% to 60%.

  Preferably, the density of the biocomposite composition for use in the present invention is, in at least some embodiments, between 1 and 2 g / mL. More preferentially, the density is between 1.2 and 1.9 g / mL. Most preferentially, the density is between 1.4 and 1.8 g / mL.

  The diameter of reinforcing fibers for use with the reinforced biocomposite medical implant may be in the range of 1 to 100 μm. Preferably, the fiber diameter is in the range of 1 to 20 μm. More preferably, the fiber diameter is in the range of 4 to 16 μm.

  The standard deviation of fiber diameter between fibers in the medical implant is preferably less than 5 μm, more preferably less than 3 μm and most preferably less than 1.5 μm. The uniformity of fiber diameter is beneficial for consistent properties throughout the implant.

  Optionally and preferably, the fiber reinforced biodegradable composite in the implant has a flexural modulus of more than 5 GPa and a flexural strength of more than 80 MPa.

  Preferably, the fiber reinforced biodegradable composite in the implant has a flexural strength in the range of 150 to 800 MPa, more preferably 150 to 400 MPa. The elastic modulus is preferably in the range of 5 to 27 GPa, more preferably 10 to 27 GPa.

  Preferably, the fiber reinforced composite within the implant retains a modulus of greater than 10 GPa after 8 weeks of implantation and a flexural strength of greater than 150 MPa after 8 weeks.

  According to the invention, in at least some embodiments, the biodegradable polymer is a copolymer or terpolymer, for example polylactide (PLA), poly-L-lactide (PLLA), poly-DL-lactide (PLLLA); Polyglycolide (PGA); glycolide copolymer, glycolide / trimethylene carbonate copolymer (PGA / TMC); lactide / tetramethyl glycolide copolymer, lactide / trimethylene carbonate copolymer, lactide / d-valerolactone copolymer, lactide / ε-caprolactone copolymer L-lactide / DL-lactide copolymer, glycolide / L-lactide copolymer (PGA / PLLA), other copolymers of PLA such as polylactide-co-glycolide; lactide / glycolide / trime Terpolymers of PLA such as lene carbonate terpolymer, lactide / glycolide / ε-caprolactone terpolymer, PLA / polyethylene oxide copolymer; polydepsipeptides; unsymmetrical-3,6-substituted poly-1,4-dioxane-2,5-diones (Polyhydroxyalkanoate; polyhydroxybutyrate) PHB) and the like; PHB / b-hydroxyvalerate copolymer (PHB / PHV); poly-b-hydroxypropionic acid (PHPA); poly-p-dioxanone (PDS); -D-valerolactone-poly-ε-caprolactone, poly (ε-caprolactone-DL-lactide) copolymer, methyl methacrylate-N-vinylpyrrolidone copolymer, polyesteramide, polyester of oxalic acid, polydihydropyran, Polyalkyl-2-cyanoacrylate; Polyurethane (PU); Polyvinyl alcohol (PVA); Polypeptide; Poly-b-malic acid (PMLA): Poly-b-alkanoic acid; Polycarbonate; Polyorthoester; Acid salts; poly (ester anhydrides); and mixtures thereof; and natural polymers such as sugars; starches, celluloses and cellulose derivatives, polysaccharides, collagens, chitosans, fibrins, hyaluronic acid, polypeptides and proteins May be there. Any of the above polymers and mixtures of their various forms may also be used.

  The biodegradable composite is preferably incorporated into the polymer matrix and may optionally include any of the above-mentioned polymers. Optionally and preferably, it is PLLA (poly-L-lactide), PDLLA (poly-DL-lactide), PLDLA, PGA (poly-glycolic acid), PLGA (poly-lactide-glycolic acid), PCL (polycaprolactone) ), PLLA-PCL, and combinations thereof. If PLLA is used, preferably the matrix comprises at least 30% PLLA, more preferably 50% and most preferably at least 70% PLLA. If PDLA is used, preferably the matrix comprises at least 5% PDLA, more preferably at least 10%, most preferably at least 20% PDLA.

  Preferably, the intrinsic viscosity (IV) (independent of the reinforcing fibers) of the polymer matrix is in the range of 1.2 to 2.4 dl / g, more preferably in the range of 1.5 to 2.1 dl / g, and most preferably Is in the range of 1.7 to 1.9 dl / g.

  Intrinsic viscosity (IV) is a viscometric method for measuring molecular size. IV is based on the flow time of the polymer solution through the capillary relative to the flow time of the pure solvent through the thin capillary.

  The mineral composition may optionally include β-tricalcium phosphate, calcium phosphate, calcium sulfate, hydroxyapatite or bioresorbable glass (also known as bioglass).

The bioabsorbable glass fibers may optionally have an oxide composition in the following mole% range:
Na2O: 11.0 to 19.0 mol%
CaO: 9.0 to 14.0 mol%
MgO: 1.5 to 8.0 mol%
B2O3: 0.5 to 3.0 mol%
Al2O3: 0 to 0.8 mol%
P2O3: 0.1 to 0.8 mol%
SiO2: 67 to 73 mol%

More preferably, it may have the following mole% range:
Na2O: 12.0 to 13.0 mol%
CaO: 9.0 to 10.0 mol%
MgO: 7.0 to 8.0 mol%
B2O3: 1.4 to 2.0 mol%
P2O3: 0.5 to 0.8 mol%
SiO2: 68 to 70 mol%

  Additional optional glass fiber compositions have already been described by Lehtonen TJ et al. (Acta Biomaterialia 9 (2013) 4868-4877), which is hereby incorporated by reference in its entirety; such glass fiber compositions are It may be optionally used instead of or in addition to the above composition.

  Additional optional bioabsorbable glass compositions are described in the following patent applications and are incorporated herein as if fully described herein by reference, and are owned in common with the present application: And shares the inventor: a biocompatible composite material and its use (WO2010122098); and an absorbable and biocompatible fiberglass composition and their use (WO2010122019).

  In a more preferred embodiment of the invention, the reinforcing filler is attached to the bioresorbable polymer such that the reinforcing effect is sustained for a long time. Such an approach is described in US 2012/0040002 A1 and EP 2243500 B1 and discusses composite materials comprising a biocompatible glass, a biocompatible matrix polymer and a coupling agent capable of forming a covalent bond. .

Optionally, the fibers are preferably at an angle to the longitudinal axis such that most of the reinforcing fibers are arranged at an angle of less than 90 °, alternatively less than 60 ° or optionally less than 45 ° from the longitudinal axis That is, they may be arranged diagonally).
Structure of medical implant composites

  The implant may be selected from the group comprising orthopedic pins, screws, plates, intramedullary rods, hip replacement parts, knee replacement parts, meshes etc.

  The average thickness of the implant is preferably in the range 0.2 to 10 mm, more preferably in the range 0.4 to 5 mm, more preferably in the range 0.5 to 2 mm and most preferably 0.5 to 1.5 mm. It is a range.

  The implant preferably comprises between 2 and 20 composite tape layers, more preferably between 2 and 10 layers and most preferably between 2 and 6 layers.

  If desired, the implant may include reinforcing ribs, gussets or posts.

  The thickness of the base of the rib is preferably less than 100% of the adjacent wall thickness. More preferably, the thickness is less than 85% and most preferably less than 75%. The thickness of the base of the rib is preferably more than 20% of the adjacent wall thickness, more preferably more than 30% and most preferably more than 50% of the adjacent wall thickness.

  Preferably, the height of the ribs is at least 2.0 times the adjacent wall thickness, more preferably at least 3.0 times the wall thickness.

  The draft of the reinforcing ribs is preferably between 0.2 and 0.8 °, more preferably between 0.4 and 0.6 °.

  Preferably, the distance between the ribs is at least twice the adjacent wall thickness. More preferably, it is at least three times the adjacent wall thickness.

  Preferably, the reinforcing ribs or other elements increase the flexural rigidity of the implant by at least 20% without increasing the compressive or tensile stiffness by more than 10%.

  If desired, the ribs along one axis, eg, the longitudinal axis of the implant, are longer than the ribs along the vertical axis, eg, the latitudinal axis of the implant, to facilitate easy insertion of the implant.

  If desired, the implant may include one or more bosses for insertion into the screw. Preferably, the boss is between 2 and 3 times the screw diameter for self tapping screw applications. The boss may further include auxiliary gussets or ribs.

  If desired, one or more sides of the implant may be textured.

If desired, the implant may include continuous fibers arranged in a circular arrangement around holes such as screws or pin holes in the implant.
Holed implant part wall

  In some medical implants, it is desirable to encapsulate cells or tissues through the implant in order to enhance the incorporation of the implant into the tissue and to increase the fit of the implant in physiological functions. It is beneficial to have gaps or holes in the wall of the medical implant described herein to further promote such inclusion growth.

  Preferably, if present, such perforations in the wall of the implant comprise at least 10%, more preferably at least 20%, at least 30%, at least 40% of the surface area of the implant or at least 50% of the surface area of the implant.

  In one optional embodiment of the invention, the implant is a screw and the holes in the screw include perforations.

  In one embodiment of the invention, the implant comprises perforations between the composite tapes or between reinforcing fibers in the composite tape making the implant.

In a preferred embodiment, the majority of the perforations are between the reinforcing fibers and do not penetrate the reinforcing fibers.
Bone filler filled cage

  In another embodiment of the invention, the implant comprises an orthopedic implant, wherein the implant forms a partial or complete container and the osteoconductive or osteoinductive material is contained within the implant container.

  In a preferred embodiment, the implant container is further perforated to allow for the improvement of bone encapsulation in osteoconductive or osteoinductive material contained within the implant cage.

  In one optional embodiment, the implant includes an opening or a lid through which bone filler can be introduced and / or bone ingrowth can occur.

In an optional embodiment, the implant comprises two or more separate parts or discrete parts joined by a joint, the cage of the implant being filled with a bone filler material and subsequently assembled or closed The bone filler may be confined inside.
Framework of continuous fiber reinforced structure with non-reinforcing surrounding material

  A continuous fiber reinforced bioabsorbable composite structure provides optimal mechanical strength and stiffness for medical implants but can not be made from continuous fiber reinforced composite tape It may also be beneficial in certain cases with additional features or layers in In such cases, the mechanical strength of the continuous fiber reinforced bioabsorbable composite structure can be incorporated into the implant, but an additional portion or layer of non-reinforcing polymer is added to improve the implant You may adjust individually. These parts or layers are preferably added to the implant either by overmolding on the structure or by 3-D printing on the structure.

  In one embodiment of the present invention, a medical implant comprises a structural support of continuous fiber reinforced bioabsorbable composite material and further comprises a portion or layer of non-reinforced polymer material.

  Optionally, the second layer functions as a bone interface layer of non-reinforcing resorbable polymeric material. Also, if desired, the structural support and the non-reinforced polymer portion are each manufactured using different manufacturing techniques. Also optionally, the structural support is made by machining, compression molding or composite flow molding, the interface layer is made by injection molding or 3D printing; optionally, the interface layer is a preformed structural support top Manufactured in

  Optionally, the non-reinforcing polymer portion is a bone interface layer, and the dimensions of the interface layer are partially or totally determined by the geometry of the bones of a particular patient or patient population.

  Optionally, the geometry of the bone in the patient or patient population is determined by measuring through imaging techniques such as X-Ray, CT, MRI.

  If desired, the modulus of elasticity and / or the flexural strength of the structural support is at least 20% greater than that of the non-reinforced polymer part.

  Optionally, the continuous fiber reinforced composite material in the implant is coated with a polymer resin and the polymer resin on the fibers in the composite material has a melting temperature higher or lower than the flowable matrix resin; or The polymer resin on the fiber has a slower or faster degradation rate than the flowable matrix resin; or the polymer resin on the fiber is more hydrophobic or more hydrophilic than the flowable matrix resin.

  In any one embodiment, the additional part or layer consists of a reinforced polymer, but the polymer is preferably reinforced by fibers less than 10 mm in length and more preferably discontinuous fibers less than 5 mm in length Ru.

  In an optional embodiment, the additional portion or layer of the non-reinforcing polymer or the discontinuous fiber-reinforced polymer further comprises an additive.

  Optionally, the additive comprises an osteoconductive material such as beta-tricalcium phosphate, calcium phosphate, hydroxyapatite, decellularized bone, or a combination of osteoconductive materials.

Optionally, the additive comprises an anti-microbial agent or an osteogenic agent.
Production method

  The continuous fiber reinforced bioabsorbable implant may optionally be manufactured using any method known in the art. Methods may include compression molding, injection molding, extrusion, machining or any combination of these methods.

  Preferably, the water content of the implant after manufacture is less than 50%, more preferably less than 1%, even more preferably less than 0.4%, less than 0.2%.

  Low water content is important to prevent degradation of the implant during storage.

  Preferably, the content of residual monomers in the implant after manufacture is less than 3%, preferably less than 2% and more preferably less than 1%.

While not wishing to be limited by a single hypothesis, if the mineral content is high relative to the biocomposite implant, then the polymer component will be largely due to the fact that the monomer component does not contribute to the mechanical function of the implant. It is particularly important to consist of polymers having low monomer components.
Implant in contact with surrounding tissue

In one optional embodiment of the invention, less than 100% of the surface area of the implant is in contact with the surrounding tissue. This may be clinically desirable for several reasons:
1. Reduction of friction with surrounding tissue during insertion, easy insertion The reduction in bone contact can reduce the bone surface interference with blood flow.

  In a preferred embodiment, the implant comprises a surface protruding portion at least 0.1 mm in height and less than 2 mm in height in contact with the tissue surrounding the implant.

Preferably, the total percentage of surface area at the implant in contact with surrounding tissue is less than 80%, more preferably less than 60%, 50%, 40%, 30%.
balloon

In one optional embodiment of the invention, the implant further comprises a balloon. The balloon wall preferably consists of between 1 and 3 layers of reinforced composite material.
Manufacture of implant

Any of the above bioabsorbable polymers or reinforced bioabsorbable polymers may be manufactured into any desired physical form for use with the present invention. The polymer substrate may be manufactured, for example, by compression molding, casting, injection molding, pultrusion, extrusion, filament winding, composite flow molding (CFM), machining or any other manufacturing technique known to one skilled in the art . The polymer may be made in any shape, such as, for example, plates, screws, nails, fibers, sheets, rods, staples, clips, needles, tubes, foams or any other shape suitable for medical devices.
Load-bearing mechanical strength

  The present invention relates to bioresorbable composites that can be used in medical applications, in particular requiring high strength and stiffness compared to bone stiffness. These medical applications require medical implants that bear all or part of the load applied by or to the body and can therefore be generally referred to as "load bearing" applications. These include fracture fixation, tendon reattachment, joint replacement, spinal fixation and spinal cages.

Preferred flexural strengths for the load-bearing medical implants described herein are at least 100 MPa, preferably more than 400 MPa, more preferably more than 600 MPa and even more preferably more than 800 MPa. The elastic modulus (or Young's modulus) of the bioresorbable composite material for use with the present invention is preferably at least 6 GPa, more preferably more than 15 GPa and even more preferably more than 20 GPa, but not more than 100 GPa, preferably not more than 60 GPa is there.
Sustained mechanical strength

  There is a need for a bioabsorbable load bearing medical implant in the present invention that maintains mechanical properties (high strength and stiffness) over time to allow sufficient bone healing. The strength and stiffness preferably exceed the strength and stiffness of cortical bone in vivo (i.e., the physiological environment), for at least three months, preferably at least six months and even more preferably at least nine months, approximately 150 to about each. Maintain 250 MPa and 15-25 GPa.

  More preferably, the flexural strength is maintained above 400 MPa, even more preferably above 600 MPa.

  In another embodiment of the present invention, the rate of degradation of the mechanical strength of the medical implant is close to the rate of material degradation of the implant as measured by the weight loss of the biodegradable composite.

  In a preferred embodiment, the implant maintains more than 50% of its mechanical strength after 3 months of implantation, while more than 50% of material degradation and hence weight loss occurs within 12 months of implantation.

  In a preferred embodiment, the implant maintains more than 70% of its mechanical strength after 3 months of implantation, while more than 70% of material degradation and hence weight loss occurs within 12 months of implantation.

  In a preferred embodiment, the implant maintains more than 50% of its mechanical strength after 6 months of implantation, while more than 50% of material degradation and hence weight loss occurs within 9 months of implantation.

  In a preferred embodiment, the implant maintains more than 70% of its mechanical strength after 6 months of implantation, while more than 70% of material degradation and hence weight loss occurs within 9 months of implantation.

  The decrease in mechanical strength and material degradation (weight loss) rate of the medical implant can be measured after in vivo implantation or after in vitro mock implantation. In the case of in vitro mock transplantation, the mock experiments may be performed in real time or by criteria of accelerated degradation.

  As used herein, "biodegradable" is a general term that includes materials, such as polymers, which are broken by discrete degradation in vivo. The decrease in mass of biodegradable material in the body may be the result of a passive process catalyzed by physicochemical conditions (eg, humidity, pH value) in the host tissue. In a preferred embodiment of the biodegradability, for the reduction of the mass of biodegradable material in the body, for simple filtration of decomposition by-products, or the metabolism of the material ("Bioresorption" or "Bioabsorption" ))) Can be removed through any natural pathway. In any case, the reduction in mass can result in partial or total elimination of the initial foreign body. In a preferred embodiment, the biodegradable composite material comprises a biodegradable polymer that cleaves by macromolecular degradation in an aqueous environment.

  A polymer is "absorbable" within the meaning of the present invention if it can be broken down into small nontoxic segments which can be metabolized or removed from the body without adverse effects. Generally, absorbable polymers swell, hydrolyze, and degrade when exposed to body tissue, resulting in significant weight loss. The hydrolysis reaction may optionally be catalyzed enzymatically. Complete bioabsorption preferably occurs within 24 months, most preferably within 12 months, but complete bioabsorption, ie, complete weight loss, may take some time.

  The term "degradation of the polymer" means a reduction in the molecular weight of the respective polymer. Preferably, for polymers used within the scope of the present invention, said degradation is caused by free water due to cleavage of the ester bond. For example, the degradation of the polymers used for the biomaterials described in the examples follows the principle of bulk erosion. Thereby, a continuous decrease in molecular weight leads to a very pronounced mass loss. The mass loss is due to the solubility of the degradation products. Methods for determining water-induced polymer degradation are well known in the art, such as titration of degradation products, viscosity measurements, differential scanning calorimetry (DSC), and the like.

The term "biocomposite" as used herein is a composite formed by a matrix and a reinforcement of fibers, both matrix and fibers being biocompatible and optionally bioresorbable. In most cases, the matrix is a polymeric resin, more particularly a rigid bioabsorbable polymer. The fibers are optionally and preferably different types of materials (ie non-synthetic bioabsorbable polymers) and may optionally include minerals, ceramics, cellulosics or other types of materials.
Clinical use

  The medical implants discussed herein are generally used for fracture reduction and fixation to restore anatomic relationships. Such fixation optionally and preferably includes one or more, more preferably all, of stable fixation, maintenance of blood supply to bone and surrounding soft tissue, and early active mobilization of parts and patients.

There are several exemplary, illustrative, non-limiting types of bone fixation implants that the materials and concepts described in accordance with at least some embodiments of the present invention may be related as follows.
Bone plate

  Bone plates are typically used to keep different portions of a fractured or otherwise cut bone firmly fixed to one another during and / or after the healing process to repair the bones together. . The bones of the limbs comprise a diaphysis with heads at both ends. The diaphysis is generally elongated and relatively cylindrical in shape.

  It is known to provide a bone plate that is attached to the diaphysis or head and diaphysis of a fractured bone to maintain two or more portions of the bone in a fixed position relative to one another. Such bone plates generally have a shape having opposite substantially parallel sides and a plurality of holes extending between the opposite sides, the holes receiving pins or screws for attaching the plate to the bone piece Suitable for

In order for the bone plate to function properly, securing different portions of the fractured bones together, the plate must be of sufficient mechanical strength and rigidity to maintain the position of the bone fragments or bone fragments. However, these mechanical properties must be achieved within thin thickness properties to ensure that the bone plate has enough space to fit snugly between the bone and the surrounding soft tissue. The thickness of the bone plate is generally in the range of 2.0 mm to 8.0 mm, more generally in the range of 2.0 mm to 4.0 mm. However, the width of the plate is variable.
screw

  Screws are used for internal bone fixation and there are various designs based on the type of fracture and the use of the screw. The screws are of different sizes for use with bones of different sizes. Screws can be used alone as well as with plates, rods or nails to support fractures. After the bone has healed, the screw may be left in place or removed.

The screw is threaded, but the threaded portion can be either fully or partially. The screws may include compression screws, fixed screws and / or cannulated screws. The diameter of the external screw can be as small as 0.5 or 1.0 mm, but generally less than 3.0 mm for small bone fixation. Large bone cortical screws can be up to 5.0 mm, while cancellous screws can reach as much as 7-8 mm. Some screws are self tapping and others require drilling before screw insertion. In the case of a cannulated screw, the central hollow portion is generally larger than 1 mm in diameter to accommodate the guide wire.
Wire / pin

  Wires are often used to fix the bones together again. They are often used to hold together bone fragments too small to be screwed on. While they can be used in combination with other forms of internal fixation, they can be used alone to treat small bone fractures such as those found in the hands or feet. The wire or pin may have a sharpened tip on either or both sides for insertion or drilling into the bone.

"K-wire" is a specific type of wire generally made from stainless steel, titanium or nitinol, with dimensions ranging from 0.5 to 2.0 mm in diameter and 2 to 25 cm in length . The "stein manpin" is generally in the range of 2.0 to 5.0 mm in diameter and 2 to 25 cm in length. Nevertheless, the terms pins and wires for bone fixation are used interchangeably herein.
anchor

Anchors and in particular suture anchors are fasteners for securing tendons and ligaments to bone. They are anchor structures that are inserted into bone and consist of one or more eyelets, holes or loops in the anchor through which the suture passes. This ties the anchor to the suture. The anchor inserted into the bone may be a screw mechanism or an interference mechanism. The anchors are generally in the range of 1.0 to 6.5 mm in diameter.
Cable, tie, wire tie

Cables, ties or wire ties can be used to provide fixation by fastening or joining the bones together. Such an implant may support bones that can not be fixed together with penetrating screws or wires / pins, if desired, due to bone damage or the presence of the implant shaft within the bone. Generally, the diameter of such cable or tie implants is optionally in the range of 1.0 mm to 2.0 mm and preferably in the range of 1.25 to 1.75 mm. The wire tie width may optionally be in the range of 1 to 10 mm.
Nail or stick

  For some fractures of long bones, the best medical practice to support the bone fragments together is through the insertion of a rod or nail through the hollow center of the bone, which usually contains some bone marrow. Screws at both ends of the rod are used to prevent the fracture from shrinking or turning and to hold the rod in place until the fracture heals. The rod and screw may be left in the bone after healing is complete. Nails or bars for bone fixation are generally 20 to 50 cm in length and 5 to 20 mm (preferably 9 to 16 mm) in diameter. The hollow portion at the central portion of the nail or rod is generally larger than 1 mm in diameter to accommodate the guide wire.

The above optional bone fixation implants optionally include but are limited to comminuted fractures, segmental fractures, adhesion failure fractures, fractures due to bone loss, proximal and distal fractures, shaft fractures, osteotomy sites, etc. May be used to fix various fracture types that are not
Example # 1-Large Diameter Pin

The following example describes the production of large diameter orthopedic pins with reinforced biocomposites. This example shows the enhanced biocomposite with respect to flexural modulus and strength both at time zero (after manufacture) and after pseudo-decomposition associated with composition structure, geometry and composition for each type of pin It shows how different medical implant pins made of materials can have different performance characteristics.
Materials and methods

Three pin implants, 6 mm in outer diameter and 5 cm long, respectively, were manufactured using the reinforced composite material. The composite material consisted of 50% w / w, 70% or 85% w / w continuous mineral fiber reinforced PLDLA 70/30 polymer. Mineral fiber composition is approximately _{Na 2 O 14%, MgO 5.4} %, CaO 9%, B 2 O 3 2.3%, P 2 O 5 1.5%, and _SiO 2 67.8% w / It was w. Test samples were produced by compression molding the multilayer composite into tube-like molds with or without a 3 mm pin insert in the center. Each layer consisted of PLDLA polymer embedded with continuous fibers arranged in one direction. The orientation of the layers relative to the longitudinal axis of the implant is 0 ° (parallel to the longitudinal axis of the implant), 45 °, 0 °, -45 °, 0 ° in an iterative manner according to the number of layers in the implant. The Each layer was approximately 0.18 mm thick. Three pin samples were made for each pin group.

The implant samples can be prepared according to ASTM D 790 (Standard Test Methods for Flexural Properties of Unreinforced and Reinforced Plastics and Electrical Insulating Materials, http: //www.astm. The tensile test system (220Q1125-95, TestResources, Minnesota, USA) was tested according to org / Standards / D 790. htm, ASTM International, Pennsylvania, USA. The test was first and foremost modified ASTM F1635 (Standard Test Method for In Vitro Degradability Testing of Hydrolytically Degradable Polymer Resins and Fabricated Forms for Surgical Implants, http://www.astm.org/Standards/F1635.htmASTM International, USA, After simulated in vitro degradation according to PA), samples are simulated fluid (SBF), 142 Na ⁺ , 5 K ⁺ , 1.5 Mg ²⁺ , 2.5 Ca ²⁺ , 147.8 Cl ⁻ , 4.2 HCO ₃ ⁻ , 1 HPO ₄ ^{3 − 5} in 0.5SO ₄ ^2- mol / m ³ Incubate with shaking at 30 rpm for 5 days at a temperature of 0 ° C. Mechanical testing was performed using a 5 KN load cell and a suitable fixture for 3-point bending tests. The sample span was 40 mm at the beginning of the test, and the crosshead speed was set to 2 mm / min. The sample dimensions, weight and density were recorded.

Scanning electron microscopy (SEM) (FEI Quanta FEG 250, The Netherlands) images are cross sections of implant samples at several magnifications with either SE or BSE detectors, with or without Au sputtering. I got The following parameters were measured or measured using ImageJTM (NIH Image Processing Software, http://www.imagej.nih.gov/ij/, National Institute of Health, MD, USA):
1. Distance between fibers Distance between layers3. Number of fibers per layer4. Fiber diameter 5. The following parameters were measured or measured using the angle of tangent to the curvature MATLAB (http://www.mathworks.com/products/matlab/, Mathworks, MA, USA):
1. Volume distribution of fibers in the implant cross section

  Table 1a shows the results of the mechanical performance of implant pins made from three different types of reinforced composites as described above. The structural properties of these implants are described by the manufacturing method described above and their internal composition is confirmed in the relevant images. The quantification of some parameters related to the structure of the internal composition of the implant can be confirmed in Table 1b.

  The flupin sample produced at OD 6 mm, 85% w / w fibers is significantly lacking in cohesive strength, presumably due to the insufficient amount of polymer bonding between the layers of fibers. These samples failed during loading into the tensile testing system, so no mechanical property results were recorded. Images of these pins can be seen in FIGS. 27 and 28, thereby indicating that there is a large amount of fibers and no polymer.

  As can be seen in Table 1A, incubation for 5 days in 50 ° C. SBF accelerates the degradation rate to 26%, 53% and 50% w / w full pin, 70% w / w full pin and 6 mm hollow pin, respectively A reduction of 41% in modulus occurred. Incubation for 5 days in SBF at 50 ° C. accelerates the degradation rate and reduces the bending strength by 51%, 62% and 45% with 50% w / w full pin, 70% w / w full pin and 6 mm hollow pin respectively occured. Incubation for 5 days in SBF at 50 ° C. accelerates the degradation rate and reduces the maximum bending load by 50% w / w full pin, 70% w / w full pin and 6 mm hollow pin by 51%, 53% and 42% respectively Arose.

  While not wishing to be limited by a single hypothesis, the reinforcing fiber content, diameter, distribution and placement in layers identified in this example (Example 1) may be attributable or at least significantly It is considered to be a contributing factor.

In particular, with regard to reinforcing fibers, an increase in the content of reinforcing fibers is observed, as confirmed by the stronger and stiffer samples produced with 70% fibers compared to those produced with 50% fibers, It can contribute positively to the mechanical properties of the medical implant. However, 70% fiber implants appeared to lose mechanical properties more rapidly. Thus, each of these fiber quantities has potential benefits. Above some point, an excessively high fiber content can result in implant failure as observed with 85% fiber pins.
Example # 2-Small diameter pin

The following example describes the production of a small diameter orthopedic pin with a reinforced biocomposite. This example relates to the flexural modulus both at time zero (after manufacture) and after pseudo-disassembly (for example, when inserted into the body) and related to composition structure, geometry and composition for each type of pin and In terms of strength, it is shown how different medical implant pins consisting of reinforced biocomposites can have different performance characteristics.
Materials and methods

Three pin implants, 2 mm in outer diameter and 5 cm long, respectively, were manufactured using the reinforced composite material. The composite material consisted of 50% w / w or 70% w / w continuous mineral fiber reinforced PLDLA 70/30 polymer. Mineral fiber composition is approximately _{Na 2 O 14%, MgO 5.4} %, CaO 9%, B 2 O 3 2.3%, P 2 O 5 1.5% and _SiO 2 67.8% w / w was. The test samples were produced by compression molding the multilayer composite into tube-like molds with or without a 1 mm pin insert in the center. Each layer consisted of PLDLA polymer embedded with continuous fibers arranged in one direction. The orientation of the layers relative to the longitudinal axis of the implant was repeated according to the number of layers in the implant and was 0 ° (equilibrium with the longitudinal axis of the implant), 45 °, 0 °, -45 °, 0 °. Each layer was approximately 0.18 mm thick. Three pin samples were made for each pin group.

The implant samples can be prepared according to ASTM D 790 (Standard Test Methods for Flexural Properties of Unreinforced and Reinforced Plastics and Electrical Insulating Materials, http: //www.astm. The tensile test system (220Q1125-95, TestResources, Minnesota, USA) was tested according to org / Standards / D 790. htm , ASTM International, PA, USA. The tests were conducted in the first and modified ASTM F 1635 (Standard Test Method for In vitro Degradation Testing of Hydrolytically Degradable Polymer Resins and Fabricated Forms for Surgical Implants, http://www.astm.org/Standards/F1635.htm ASTM International, After simulated in vitro degradation according to the United States, Pennsylvania), samples are simulated body fluid (SBF), 142 Na ⁺ , 5 K ⁺ , 1.5 Mg ²⁺ , 2.5 Ca ²⁺ , 147.8 Cl ⁻ , 4.2 HCO ₃ ⁻ , 1 HPO ₄ ^3, odor in 0.5SO ₄ ^2- mol / ^{m 3} 5 days at a temperature of 50 ° C., and incubated with shaking at 30 rpm. Mechanical testing was performed using a 500 N load cell and a suitable fixture for 3-point bending tests. The sample span was 40 mm at the beginning of the test, and the crosshead speed was set to 2 mm / min. The sample dimensions, weight and density were recorded.

Scanning electron microscopy (SEM) (FEI Quanta FEG 250, The Netherlands) images are cross sections of implant samples at several magnifications with either SE or BSE detectors, with or without Au sputtering. I got The following parameters were measured or measured using ImageJTM (NIH Image Processing Software, http://www.imagej.nih.gov/ij/, National Institute of Health, MD, USA):
1. Distance between fibers Distance between layers3. Number of fibers per layer4. Fiber diameter 5. The following parameters were measured or measured using the angle of tangent to the curvature MATLAB (http://www.mathworks.com/products/matlab/, Mathworks, MA, USA):
1. Fiber Volume Distribution in Implant Cross Section: The ratio of fibers to polymer was calculated by summing all the fiber areas in the image and dividing by the area of the entire implant cross section in the image.
Ratio of fibers to polymer = total area of fibers Total area of cross section * 100
result

Table 2a shows the mechanical performance results for three different types of reinforced composite implant pins manufactured as described above. The structural properties of these implants are described by the manufacturing method described above and their internal composition is confirmed in the relevant images. The quantification of some parameters related to the structure of the internal composition of the implant can be confirmed in Tables 2b, c and d.

  Incubation for 5 days in SBF at 50 ° C accelerates the degradation rate and reduces the bending strength by 54%, 27% and 73% with 50% w / w full pin, 70% w / w full pin and 2 mm hollow pin respectively occured. Incubation for 5 days in 50 ° C. SBF accelerates the degradation rate and reduces the maximum bending load by 50% w / w full pin, 70% w / w full pin and 2 mm hollow pin by 52%, 27% and 71% respectively Arose. Incubation for 5 days in SBF at 50 ° C. accelerated the degradation rate, resulting in a loss of flexural modulus of 32% and 29% at 70% w / w full pin and 2 mm hollow 50% w / w pin, respectively.

  While not wishing to be limited by a single hypothesis, the content, diameter, distribution and placement in layers of reinforcing fibers identified in this example (Example 2) may be attributable or at least significantly It is considered to be a contributing factor.

This example also suggests potential structural differences between different implant component forms (between full pins and cannulated pins), and the reinforcing fiber layer in the biocomposite implant is the shape of the implant And depending on the forces to which the implant is exposed during its manufacture, it is optionally possible to arrange and arrange themselves in different ways.
Example # 3-Plate

The following example describes the production of a thin orthopedic plate having a reinforced biocomposite. This example shows the enhanced biocomposite with respect to flexural modulus and strength both at time zero (after manufacture) and after pseudo-decomposition related to composition structure, geometry and composition for each type of plate It shows how different medical implant plates of material can have different performance characteristics.
Materials and methods

Four plate implants, each having a thickness of 2 mm, a width of 12.8 mm and a length of 6 cm, were produced using the reinforced composite material. The composite material consisted of 50% w / w or 70% w / w continuous mineral fiber reinforced PLDLA 70/30 polymer. Mineral fiber composition is approximately _{Na 2 O 14%, MgO 5.4} %, CaO 9%, B 2 O 3 2.3%, P 2 O 5 1.5% and _SiO 2 67.8% w / w was. Test samples were made by compression molding the multilayer composite into a rectangular mold. Each layer consisted of PLDLA polymer embedded with continuous fibers arranged in one direction. The orientation of the layers relative to the longitudinal axis of the implant was repeated according to the number of layers in the implant and was 0 ° (equilibrium with the longitudinal axis of the implant), 45 °, 0 °, -45 °, 0 °. Each layer was approximately 0.18 mm thick. For amorphous plates, continuous fibers were cut into small pieces, mixed and shaped. Three plate samples were produced for each plate group.

The implant samples can be prepared according to ASTM D 790 (Standard Test Methods for Flexural Properties of Unreinforced and Reinforced Plastics and Electrical Insulating Materials, http: //www.astm. The tensile test system (220Q1125-95, TestResources, Minnesota, USA) was tested according to org / Standards / D 790. htm , ASTM International, PA, USA. The tests were conducted in the first and modified ASTM F 1635 (Standard Test Method for In vitro Degradation Testing of Hydrolytically Degradable Polymer Resins and Fabricated Forms for Surgical Implants, http://www.astm.org/Standards/F1635.htm ASTM International, After simulated in vitro degradation according to the United States, Pennsylvania), samples are simulated body fluid (SBF), 142 Na ⁺ , 5 K ⁺ , 1.5 Mg ²⁺ , 2.5 Ca ²⁺ , 147.8 Cl ⁻ , 4.2 HCO ₃ ⁻ , 1 HPO ₄ ^3, odor in 0.5SO ₄ ^2- mol / ^{m 3} 5 days at a temperature of 50 ° C., and incubated with shaking at 30 rpm. Mechanical testing was performed using a 5 KN load cell and a suitable fixture for 3-point bending tests. The sample span was 40 mm at the beginning of the test, and the crosshead speed was set to 2 mm / min. The sample dimensions, weight and density were recorded.

Scanning electron microscopy (SEM) (FEI Quanta FEG 250, The Netherlands) images are cross sections of implant samples at several magnifications with either SE or BSE detectors, with or without Au sputtering. I got The following parameters were measured or measured using ImageJTM (NIH Image Processing Software, http://www.imagej.nih.gov/ij/, National Institute of Health, MD, USA):
1. Distance between fibers Distance between layers3. Number of fibers per layer4. Fiber diameter 5. The following parameters were measured or measured using the angle of tangent to the curvature MATLAB (http://www.mathworks.com/products/matlab/, Mathworks, MA, USA):
1. Volume distribution of fibers in the implant cross section

  Table 3a shows the mechanical performance results for three different types of reinforced composite implant pins manufactured as described above. The structural properties of these implants are described by the manufacturing method described above and their internal composition is confirmed in the relevant images. The quantification of some parameters related to the structure of the internal composition of the implant can be confirmed in Table 3b.

  Incubation for 5 days in SBF at 50 ° C. accelerated the degradation rate, resulting in a decrease in flexural modulus of 27% and 53% for the 50% w / w full plate and the 70% w / w full plate, respectively. Incubation for 5 days in SBF at 50 ° C. accelerated the degradation rate, resulting in a 58% and 76% decrease in flexural strength for the 50% w / w and 70% w / w full plates, respectively.

  Incubation for 5 days in SBF at 50 ° C. accelerated the degradation rate, resulting in a 50% and 62% reduction in maximum bending load for 50% full plate w / w and 70% w / w full plate, respectively.

  In this geometry and manufacturing method, it is believed that increasing the fiber content from 50% to 70 w / w increases initial mechanical strength but accelerates the degradation process.

  The contrast between short unoriented fibers and continuous oriented fibers present in the amorphous plate results in a 46%, 65% and 66% reduction in modulus, flexural strength and maximum load at similar density and production conditions The

Example # 4-Decomposition Difference

The following examples describe the degradation of orthopedic implants made from reinforced biocomposites. This example shows how different medical implants consisting of reinforced biocomposites can differ in their performance characteristics with respect to material loss and swelling rate after pseudo-degradation. As intended below, the resorbable orthopedic implant for bone fixation ideally maintains its strength for the time required for the bone to heal, and then gradually as it is replaced by bone Need to break down and lose their strength. Material weight loss is an indicator of degradation rate. The swelling ratio is an indicator of conformational change, an index of hydrophilicity and an index of porosity. Control of both parameters is important for implant design.
Materials and methods

Pin and plate implants were manufactured using the reinforced composite material as described in Examples 1-3. The composite material consisted of 50% w / w or 70% w / w continuous mineral fiber reinforced PLDLA 70/30 polymer. Mineral fiber composition is approximately _{Na 2 O 14%, MgO 5.4} %, CaO 9%, B 2 O 3 2.3%, P 2 O 5 1.5% and _SiO 2 67.8% w / w was. Test samples were prepared by compression molding the multilayer composite into appropriate molds. Each layer consisted of PLDLA polymer embedded with continuous fibers arranged in one direction. The orientation of the layers relative to the longitudinal axis of the implant was repeated according to the number of layers in the implant and was 0 ° (equilibrium with the longitudinal axis of the implant), 45 °, 0 °, -45 °, 0 °. Each layer was approximately 0.18 mm thick. Three implant samples were produced for each group.

The implant samples are initially weighed and after simulated in vitro degradation according to ASTM F1635 modified, samples in simulated body fluid (SBF), 142 Na ⁺ , 5 K ⁺ , 1.5 Mg ²⁺ , 2.5 Ca 2 ⁺ , 147.8 Cl ⁻ , Incubate with shaking at 30 rpm for 5 days at a temperature of 50 ° C. in 4.2 HCO ₃ ⁻ , 1 HPO ₄ ³⁻ , 0.5SO ₄ ²⁻ mol / m ³ . The sample was then dried overnight in a vacuum desiccator and weighed again. Material loss percentage was calculated as (initial weight-dry weight) / initial weight * 100. The swelling ratio was calculated as (weight at the end of incubation-dry weight) / dry weight * 100.
result

  Table 4 shows the gravimetric results of different types of reinforced composite implants manufactured as described above.

  For 2 mm pins and plates, increasing the concentration of mineral fibers from 50% to 70% increases material loss and swelling over time by more than about 110% and 40%, respectively. The relative degradation, which is measured by relative material loss, appears to be faster for cannulated implants than for non-cannulated designs.

At 6 mm pins, increasing the concentration of mineral fibers from 50% to 70% also causes an increase in degradation as measured by% material loss. With a 6 mm cannulation pin, due to the relative degradation increase, a 74% increase in swelling for full pin may also be noted.
Example 5-Mineral Content

  In the current example, biocomposite implant samples comprising 50, 60 and 70% mineral content are shown. These samples have both high mineral content and high mechanical properties.

This example further demonstrates the difference between time = 0 and five days after simulated bioabsorption for medical implant mechanical properties. In many cases, the mechanical properties of implants with 50% mineral content (including flexural modulus, flexural strength and maximum load) are lower than those of corresponding implants with higher mineral content at time = 0 The However, after 5 days of simulated bioabsorption, the mechanical properties of implants with higher mineral content (60% or 70%) were further reduced than with 50% mineral content implants. As such, the long-term performance of the 50% mineral content implant will be improved as compared to implants of higher mineral content. However, with higher mineral content, an initially stronger implant can be achieved.
Methods and materials

Three biocomposite implants were manufactured: pins 2 mm OD, pins 6 mm OD and rectangular plates (60 x 27 x 1.5 mm). Each sample was 7 cm in length. The composite material consisted of 50% w / w, 60% w / w or 70% w / w continuous mineral fiber reinforced PLDLA 70/30 polymer. Mineral fiber composition is approximately _{Na 2 O 14%, MgO 5.4} %, CaO 9%, B 2 O 3 2.3%, P 2 O 5 1.5% and _SiO 2 67.8% w / w was. Test samples were prepared by compression molding a multilayer composite into a tubular or rectangular mold. Each layer consisted of PLDLA polymer embedded with continuous fibers arranged in one direction. The orientation of the layers with respect to the longitudinal axis of the implant was repeated according to the multiple layers in the implant and were 0 ° (equilibrium with the longitudinal axis of the implant), 45 °, 0 °, -45 °, 0 °. Each layer was approximately 0.18 mm thick. Three samples were made for each group. The mechanical properties were tested in a 3-point bending test.
result

Example 6 Additional Drawings Illustrating Various Embodiments

  FIG. 30 shows a type of continuous fiber reinforced tape that can be used to form a layer in a medical implant consisting of a continuous fiber reinforced layer. Top view (3000) shows a single strip of composite tape comprising reinforcing fibers aligned in a single direction within a bioabsorbable polymer matrix. Reinforcing fibers (3006) interspersed within the bioabsorbable polymer matrix (3008) can be seen more clearly in the enlarged top view (3002) of the continuous fiber reinforced composite tape. The reinforcing fibers may be present as separate fibers or bundles of several reinforcing fibers per bundle. A cross-sectional view of continuous fiber reinforced tape (3004) shows bundles of aligned reinforcing fibers (3010) embedded within a bioabsorbable polymer matrix (3012). It is preferred that the fibers do not break the surface of the bioabsorbable polymer matrix.

  FIG. 31 shows a cutaway three-dimensional view of a continuous fiber reinforced tape (200). The cutaway shows aligned reinforcing fibers (202) embedded within a bioabsorbable polymer matrix (204).

  Figure 32a shows a top view of a reinforced bioabsorbable composite sheet (300) consisting of three layers of unidirectional fibers at different angles. Each layer may optionally consist of a continuous fiber reinforced tape of the type shown in FIG. The magnified view (302) shows layers of unidirectional fibers at different angles within the implant. One layer (304) is aligned with the longitudinal axis, one layer (306) is aligned with the right angle of the longitudinal axis, and one layer (308) with the left angle of the longitudinal axis Arranged.

  FIG. 32 b shows a cutaway view of a reinforced bioabsorbable composite structure (310) consisting of three layers of unidirectional fibers of different angles. One layer (312) is aligned with the longitudinal axis, one layer (314) is aligned with the right angle of the longitudinal axis, and one layer (316) with the left angle of the longitudinal axis Arranged. Each layer consists of reinforced continuous fibers (318) embedded in a bioabsorbable polymer matrix (320).

  FIG. 33 shows the wall of a continuous fiber reinforced composite medical implant. The wall of the implant consists of two layers of composite fiber layers (402 and 404) reinforced with unidirectional continuous fibers arranged at an angle perpendicular to one another. The wall of the medical implant additionally comprises perforations (406) which allow the penetration of tissue into or through the implant.

  Figure 34 is a continuous fiber reinforced composite medical implant further including perforations (502) that allow for the ingrowth of tissue and cells into the bone filler material (504) contained within the bone filler cage. Bone filler cage consisting of walls (500) is shown. The bone filler cage optionally includes a separate lid for closing the cage (506).

Figure 35 shows a bioabsorbable cannulated screw (600), a two-part medical implant: a cylindrical core (602) of a continuous fiber reinforced bioabsorbable composite and subsequently continuous Threaded portion (604) of bioabsorbable polymer molded or 3D printed onto the core of the fiber. While this provides a significant amount or most of the mechanical strength provided by the continuous fiber reinforced portion that serves as mechanical support or structure, the additional implant features are reinforced with continuous fiber An example of a bioabsorbable medical implant that can be molded or printed directly onto a fiber reinforced composite material that is not of a material.
Example 7-Mineral Content

In the current example, biocomposite implant samples comprising 50, 60 and 70% mineral content are shown. These samples have both high mineral content and high mechanical properties.
Methods and materials

Three biocomposite implants were manufactured: pins 2 mm OD, pins 6 mm OD and rectangular plates (60 x 27 x 1.5 mm). Each sample was 7 cm in length. The composite material consisted of 50% w / w, 60% w / w or 70% w / w continuous mineral fiber reinforced PLDLA 70/30 polymer. The mineral fiber composition was approximately 14% Na2O, 5.4% MgO, 9% CaO, 2.3% B2O3, 1.5% P2O5 and 67.8% w / w SiO2. Test samples were prepared by compression molding a multilayer composite into a tubular or rectangular mold. Each layer consisted of PLDLA polymer embedded with continuous fibers arranged in one direction. The orientation of the layers with respect to the longitudinal axis of the implant was repeated according to the multiple layers in the implant and were 0 ° (equilibrium with the longitudinal axis of the implant), 45 °, 0 °, -45 °, 0 °. Each layer was approximately 0.18 mm thick. Three samples were made for each group. The mechanical properties were tested in a 3-point bending test.
result

Example 8-Mineral Content and Sustained Strength

In the current example, biocomposite implant samples comprising 58% and 68% mineral content are shown. These samples have both high mineral content and high mechanical properties.
Methods and materials

Biocomposite rectangular plate implants were produced with dimensions of 12.7x60x2.0 mm. The composite material consisted of 58% w / w or 68% w / w mineral fiber reinforced PLDLA 70/30 polymer. Mineral fiber composition is approximately _{Na 2 O 14%, MgO 5.4} %, CaO 9%, B 2 O 3 2.3%, P 2 O 5 1.5% and _SiO 2 67.8% w / w was. Test samples were produced by compression molding the composite into rectangular molds. Reinforcing mineral fibers were of a cut nature, the length of the fiber portion being mainly in the range of 5 to 10 mm. The plate weight averaged 2.75 g for each plate. Ten samples were made for each group. The mechanical properties were tested in a three point bending test according to ASTM D 790, and five samples from each of the 58% and 68% groups were tested at time zero (t = 0 days), 58% and 68% Five samples from each of the following groups were tested in PBS after 5 days of simulated in vitro degradation according to modified ASTM F 1635 (37 ° C., 60 rpm, t = 5 days).

Mechanical testing was performed using a 5 KN load cell and a suitable fixture for 3-point bending tests. The sample span was 40 mm at the beginning of the test, and the crosshead speed was set to 2 mm / min. The dimensions and weight of the sample were recorded.
result

  The 58% mineral plate had a slightly higher flexural strength at T0 than the 68% plate. After 5 days under identical conditions in PBS solution, the flexural strength of the 58% plate was reduced by 32%, while the flexural strength of the 68% plate was reduced by 42%. This test was conducted after only a few days of pseudo-decomposition, but an increase in fiber content above 60% suggests that it reduces the flexural strength and increases the rate of decrease in mechanical strength over time There is a clear tendency.

  It will be understood that various features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination. It will be understood by those skilled in the art that the present invention is not particularly limited by what has already been shown and described herein. Rather, the scope of the present invention is limited only by the following claims.

Claims (114)

  A medical implant comprising a biocomposite, the biocomposite comprising a polymer and a plurality of reinforcing fibers, wherein the weight percentage of the mineral composition in the biocomposite medical implant is 40-90% A medical implant, wherein the mean diameter of the fibers is in the range of 1 to 100 micrometers.   The implant of claim 1, wherein the weight percent is in the range of 40% to 70%.   The implant according to claim 2, wherein the weight percentage is in the range of 40% to 65%.   The implant according to claim 3, wherein the weight percentage is in the range of 45% to 60%.   The implant according to any one of claims 1 to 4, wherein the mineral composition is silica based. The implant according to claim 5, wherein the silica-based mineral compound has a composition of at least one oxide in at least one of the following mole% ranges:
Na ₂ O: 11.0 to 19.0 mol%
CaO: 9.0 to 14.0 mol%
MgO: 1.5 to 8.0 mol%
B ₂ O ₃ : 0.5 to 3.0 mol%
Al ₂ O ₃ : 0 to 0.8 mol%
P ₂ O ₃ : 0.1 to 0.8 mol%
SiO ₂ : 67 to 73 mol% The implant according to claim 6, wherein the silica-based mineral compound has at least one oxide composition in at least one of the following mole% ranges:
Na ₂ O: 12.0 to 13.0 mol%
CaO: 9.0 to 10.0 mol%
MgO: 7.0 to 8.0 mol%
B ₂ O ₃ : 1.4 to 2.0 mol%
P ₂ O ₃ : 0.5 to 0.8 mol%
SiO ₂ : 68 to 70 mol%   The implant according to any of the preceding claims, wherein the density of the biocomposite composition is between 1 and 2 g / mL.   9. An implant according to claim 8, wherein the density is between 1.2 and 1.9 g / mL.   The implant according to claim 9, wherein the density is between 1.4 and 1.8 g / mL.   11. An implant according to any of the preceding claims, wherein the mineral content is provided by reinforced mineral fibers made from the mineral composition.   The implant according to claim 11, wherein the diameter of the majority of reinforcing fibers is in the range of 0 to 100 μm.   The implant according to claim 12, wherein the diameter is in the range of 1 to 20 μm.   14. An implant according to claim 13, wherein the diameter is in the range of 4 to 16 [mu] m.   15. An implant according to claim 14, wherein the diameter is in the range of 9 to 14 [mu] m.   The implant according to any one of claims 11 to 15, wherein the standard deviation of fiber diameter between fibers in the medical implant is less than 5 μm.   17. An implant according to claim 16, wherein the standard deviation is less than 3 [mu] m.   18. The implant of claim 17, wherein the standard deviation is less than 1.5 [mu] m.   12. The reinforcing fiber comprises fiber portions within a polymer matrix, the polymer is biodegradable and the biodegradable polymer is incorporated into a biodegradable composite to form the matrix. 18. An implant according to any one of 18.   20. An implant according to claim 19, wherein the mean fiber length and / or the majority of the fiber length is in the range of 0.5 to 20 mm.   21. An implant according to claim 20, wherein the length is in the range of 1-15 mm.   22. An implant according to claim 21, wherein the length is in the range of 3-10 mm.   The implant according to claim 22, wherein the length is in the range of 4-8 mm.   24. An implant according to any one of claims 11-23, wherein the fibers are embedded in a polymer matrix comprising the biocomposite.   The polymer is lactide, glycolide, caprolactone, valerolactone, carbonate (eg, trimethylene carbonate, tetramethylene carbonate, etc.), dioxanone (eg, 1,4-dioxanone), δ-valerolactone, 1, dioxepanone), for example, 1,4-dioxepan-2-one and 1,5-dioxepan-2-one), ethylene glycol, ethylene oxide, ester amide, γ-hydroxyvalerate, β-hydroxypropionic acid, α-hydroxy acid, hydroxy Buterate, poly (ortho ester), hydroxyalkanoate, tyrosine carbonate, polyimide carbonate, poly (bisphenol A-iminocarbonate) and poly (hydroquinone-iminocarbo) Such as polyiminocarbonate polyurethanes, polyanhydrides, polymeric drugs (eg, polydiflunisal, polyaspirin and protein therapeutics), sugars; starches, celluloses and cellulose derivatives, polysaccharides, collagen, chitosan, fibrin, hyaluronic acid, Polypeptides, proteins, poly (amino acids), polylactides (PLA), poly-L-lactides (PLLA), poly-DL-lactides (PDLLA); polyglycolides (PGA); copolymers of glycolide, glycolide / trimethylene carbonate copolymers PGA / TMC); lactide / tetramethyl glycolide copolymer, lactide / trimethylene carbonate copolymer, lactide / d-valerolactone copolymer, lactide / ε-caprolactone copolymer, L- Other copolymers of PLA such as lactide / DL-lactide copolymer, glycolide / L-lactide copolymer (PGA / PLLA), polylactide-co-glycolide; lactide / glycolide / trimethylene carbonate terpolymer, lactide / glycolide / ε-caprolactone ter Polymers, PLA terpolymers such as PLA / polyethylene oxide copolymers; polydepsipeptides; unsymmetrical-3,6-substituted poly-1,4-dioxane-2,5-diones; polyhydroxyalkanoates; polyhydroxybutyrate (PHB) Etc .; PHB / b-hydroxyvalerate copolymers (PHB / PHV); poly-b-hydroxypropionic acid (PHPA); poly-p-dioxanone (PDS); poly-d-valerolactone-poly-ε-ka Lolactone, poly (ε-caprolactone-DL-lactide) copolymer, methyl methacrylate-N-vinylpyrrolidone copolymer, polyesteramide, polyester of oxalic acid, polydihydropyran, polyalkyl-2-cyanoacrylate, polyurethane (PU), polyvinyl alcohol (PVA); Polypeptide; Poly-b-malic acid (PMLA): Poly-b-alkabic acid; Polycarbonate; Polyorthoester; Polyphosphate; Poly (ester anhydride); An implant according to claim 24, comprising as well as their derivatives, copolymers and mixtures thereof.   26. The implant of claim 25, wherein the polymer is selected from the group consisting of PLLA, PDLA, PGA, PLGA, PCL, PLLA-PCL, and combinations thereof.   27. An implant according to claim 26, wherein the PLLA is used for the polymer matrix and the matrix comprises at least 30% PLLA.   28. The implant of claim 27, wherein the matrix comprises at least 50% PLLA.   29. The implant of claim 28, wherein the matrix comprises at least 70% PLLA.   30. An implant according to claim 29, wherein the PDLA is used for the polymer matrix, the matrix comprising at least 5% PDLA.   31. The implant of claim 30, wherein the matrix comprises at least 10% PDLA.   32. The implant of claim 31, wherein the matrix comprises at least 20% PDLA.   33. An implant according to any one of the preceding claims, comprising a heterogeneous structure.   34. An implant according to claim 33, wherein the heterogeneous structure is continuous.   34. The implant of claim 33, comprising multiple layers.   36. The implant of claim 35, wherein the layer is amorphous.   36. The implant of claim 35, wherein the fibers are unidirectionally arranged in each layer.   An implant according to claim 37, wherein the arranged fibers comprise arranged fiber portions of 5 to 12 mm in length on average.   38. An implant according to claim 37, wherein the arranged fibers are continuous.   40. An implant according to any of the preceding claims, comprising between 1 and 100 reinforcing fibers in each biocomposite layer.   41. The implant of claim 40, comprising between 2 and 40 reinforcing fibers in each biocomposite layer.   42. An implant according to claim 41, comprising between 4 and 20 reinforcing fibers in each biocomposite layer.   The orientation of the fibers is such that each layer has a fiber orientation in a particular direction, each adjacent layer is at a different angle, and the angular difference between the layers is between 15 and 75 degrees, 43. An implant according to any one of the preceding claims, which alternates between adjacent layers.   44. An implant according to claim 43, wherein the angular difference between the layers is between 30 and 60 degrees.   45. An implant according to claim 44, wherein the angular difference between the layers is between 40 and 50 degrees.   An implant according to any one of the preceding claims, wherein the distance between the layers, determined by the distance between the last fiber in one layer and the first fiber in the adjacent layer, is between 0 and 200 μm. .   47. An implant according to claim 46, wherein the distance is between 0 and 60 [mu] m.   48. An implant according to claim 47, wherein the distance is between 1 and 40 [mu] m.   49. An implant according to claim 48, wherein the distance is between 2 and 30 [mu] m.   50. An implant according to any one of the preceding claims, wherein the fibers are continuous fibers.   51. The implant of claim 50, wherein the continuous fibers are longer than 4 mm.   52. An implant according to claim 51, wherein the continuous fibers are longer than 8 mm.   53. The implant of claim 52, wherein the continuous fibers are longer than 12 mm.   54. The implant of claim 53, wherein the continuous fibers are longer than 16 mm.   55. An implant according to claim 54, wherein the continuous fibers are longer than 20 mm.   56. An implant according to any of the preceding claims, wherein the length of at least part of the reinforcing fibers in the fibers is at least 50% of the longitudinal length in the implant.   57. The implant of claim 56, wherein the length of the majority of the reinforcing fibers in the fibers is at least 50% of the longitudinal length of the implant.   58. An implant according to claim 56 or 57, wherein the length of the reinforcing fibers is 60% of the longitudinal length of the implant.   59. The implant of claim 58, wherein the length of the reinforcing fiber is 75% of the longitudinal length of the implant.   60. An implant according to any of the preceding claims, wherein the majority of reinforcing fibers in the composite layer are aligned with the longitudinal axis of the medical implant.   61. The implant of claim 60, wherein more than 70%, 80%, 90%, 95% of the fibers are aligned in one direction along the longitudinal axis.   62. An implant according to claim 60 or 61, wherein the plurality of fibers are additionally arranged in three directions.   The implant according to claim 62, wherein a plurality of fibers are arranged in each of the following alignment options with respect to said longitudinal axis: 0 °, 30 °, -30 °, 45 °, -45 °, 90 °.   64. The implant according to claim 63, wherein a plurality of fibers are arranged in each of the following alignment options with respect to the longitudinal axis: 0 °, 45 °, -45 °, 90 °.   65. The implant according to claim 64, wherein a plurality of fibers are arranged in each of the following alignment options with respect to the longitudinal axis: 0 °, 45 °, -45 °.   66. A method according to any one of the preceding claims, wherein a majority of the fibers are arranged at the longitudinal access of the implant and a plurality of fibers are arranged in the following arrangement with respect to the longitudinal axis: Implants: 45 °, -45 °.   67. An implant according to any one of the preceding claims, wherein the diameter of the fibers is in the range 1 to 100 [mu] m.   68. An implant according to claim 67, wherein the diameter of the fibers is in the range of 1 to 20 [mu] m.   69. An implant according to claim 68, wherein the diameter of the fibers is in the range of 4 to 16 [mu] m.   69. An implant according to claim 68, wherein the diameter of the fibers is in the range of 6-20 [mu] m.   71. The implant of claim 70, wherein the diameter is in the range of 10-18 [mu] m.   72. An implant according to claim 71, wherein the diameter is in the range of 14 to 16 [mu] m.   73. An implant according to any one of the preceding claims, wherein the standard deviation of fiber diameters between fibers is less than 5 [mu] m.   74. An implant according to claim 73, wherein the standard deviation of the fiber diameter is less than 3 [mu] m.   75. An implant according to claim 74, wherein the standard deviation of the fiber diameter is less than 1.5 [mu] m.   76. An implant according to any one of the preceding claims, wherein the volume percent of reinforcing fibers in the implant is in the range of 30-90%.   78. The implant of claim 76, wherein the volume percent is in the range of 40% to 70%.   78. An implant according to any one of the preceding claims, wherein each composite layer is 0.05 mm to 0.5 mm thick.   79. An implant according to any one of the preceding claims, wherein each composite layer is 2 to 30 mm wide.   80. An implant according to any one of the preceding claims, wherein the fibers are arranged as a mesh.   The implant according to any one of the preceding claims, wherein the implant has a flexural modulus of more than 12 GPa and a flexural strength of more than 180 MPa after 5 days of pseudophysiological degradation.   82. An implant according to claim 81, wherein the implant has a flexural modulus of greater than 10 GPa and a flexural strength of greater than 120 MPa after 5 days of pseudophysiological degradation.   83. The implant of claim 82, wherein the implant has a flexural strength in the range of 400-800 MPa.   84. The implant of claim 83, wherein the implant has a flexural strength in the range of 650-800 MPa.   85. An implant according to any one of claims 82 to 84, wherein the implant has a modulus of elasticity in the range of 10 to 27 GPa.   86. An implant according to any one of claims 82-85, wherein said implant has said modulus of elasticity in the range of 16-27 GPa.   87. An implant according to any one of the preceding claims, wherein the implant retains a modulus of elasticity above 10 GPa after 8 weeks of implantation and a flexural strength above 150 MPa after 8 weeks of implantation.   88. An implant according to any one of the preceding claims, wherein the flexural modulus is greater than 15 GPa and the flexural strength is greater than 150 MPa after 3 months of in vivo implantation.   89. An implant according to any one of the preceding claims, wherein the flexural modulus is greater than 15 GPa and the flexural strength is greater than 150 MPa after 4 months of in vivo implantation.   90. An implant according to any one of the preceding claims, wherein the flexural modulus is greater than 15 GPa and the flexural strength is greater than 150 MPa after 6 months of in vivo implantation.   91. An implant according to any of the preceding claims, wherein the majority of the surface of the implant is covered.   92. An implant according to claim 91, wherein the coating is by a polymer film.   93. The implant of claim 92, wherein the surface polymer film is on average 0.5 to 50 [mu] m thick.   94. An implant according to claim 93, wherein the thickness is 5 to 50 [mu] m.   95. An implant according to claim 94, wherein the thickness is 10 to 40 [mu] m.   96. An implant according to any of the preceding claims, comprising fibers exposed to the surface of the implant, wherein the exposed fibers constitute the surface of the implant of 1-60%.   97. The implant of claim 96, wherein the exposed fibers comprise 10 to 50% of the implant surface.   100. The implant of claim 97, wherein the exposed fibers comprise 15 to 30% of the implant surface.   99. An implant according to any one of claims 1 to 98, wherein the water content of the manufactured implant is less than 50%.   100. An implant according to claim 99, wherein the water content is less than 1%.   101. An implant according to claim 100, wherein the water content is less than 0.4%.   102. An implant according to claim 101, wherein the water content is less than 0.2%.   103. An implant according to any of the preceding claims, wherein the content of residual monomers in the implant after manufacture is less than 3%.   104. An implant according to claim 103, wherein the content of residual monomer is less than 2%.   105. An implant according to claim 104, wherein the content of residual monomer is less than 1%.   Implants include other devices for such applications, such as bone fixation plates, intramedullary nails, joint (hip, knee, elbow) implants, spinal implants and fracture fixation, tendon reattachment, spinal fixation and spinal cages. 106. An implant according to any one of the preceding claims, selected from the group.   107. The implant of claim 106, wherein the implant is adapted to a threaded implant.   108. The implant of claim 107, wherein the outer layer of the threaded implant is oriented such that the direction of the fibers approaches the twist angle of the threaded portion of the threaded implant.   109. The implant of claim 108, wherein the alignment angle in the fiber direction is within 45 degrees of the twist angle.   110. An implant according to any of claims 107 to 109, wherein the threaded implant is a threaded screw.   107. The implant of claim 106, wherein the implant is adapted to a circular implant.   A method of treatment for orthopedic applications to a patient in need of such treatment comprising implanting the patient with a medical implant according to any one of claims 1 to 111.   113. The method of claim 112, wherein the implanting into the patient comprises performing structural fixation for load bearing purposes within the patient.   114. The treatment method of claim 113, wherein performing the structural fixation comprises performing bone fixation.

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